Nutraceuticals:

Nutraceutical Formulations for Enhanced Bioavailability

Antioxidant and anti-inflammatory benefits in context of enhanced by availability formulations

As part of an anti-inflammatory diet, foods may be emphasized due to their capacity for providing nutrients with anti-inflammatory and or antioxidant properties in an effort to reduce systemic inflammation and oxidative stress. Multiple nutrients have been identified in the diet that have these properties, but they may have limited by availability due to poor absorption from the gut or other variables, such as impaired ability to pass through the blood brain barrier to enter the brain or nervous system.

“Eat to live, not live to eat.”

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Definitions and Terms Related to Pain

 

Nutraceuticals

Antioxidant and anti-inflammatory benefits in context of enhanced bioavailability formulations

This section reviewed different nutraceuticals and their bioavailability along with descriptions of enhanced formulations available for supplements.

Bioavailability

Bioavailability is a measure of the fraction of a compound reaching systemic circulation and target tissues in an active form which is critical for therapeutic effectiveness. Supplemental forms of nutraceuticals are formulated to enhance bio availability via different mechanisms, including liposomal and nano particle formulations.

Factors Influencing Bioavailability and Neural Delivery

Key factors that influence by bioavailability include:

  1. Absorption from the gut:
    • This is a primary bottleneck for resveratrol (~1–5%), curcumin (~1%), and CoQ10 (~5–10%) due to poor solubility and gut barrier crossing [1, 2, 3].
    • Liposomal and nanoparticle formulations enhance absorption ~2–20-fold [4, 7].
  1. Metabolism:
    • Rapid metabolism by the liver (e.g., glucuronidation for resveratrol, curcumin) reduces active compound levels [1, 2].
    • Enhanced formulations protect against first-pass effects.
  1. Distribution:
    • Brain and nervous system delivery is critical for neuropathic pain and neuroinflammation. The blood-brain barrier (BBB) restricts polar molecules;
    • liposomal forms improve neural delivery ~2–10-fold, nanoparticles ~5–20-fold [21, 22].
  1. Excretion by the kidney or got:
    • Rapid clearance (e.g., resveratrol’s ~1–2-hour half-life) limits efficacy;
    • enhanced formulations extend duration [1].
  1. Stability:
    • Gastrointestinal degradation (e.g., curcumin at neutral pH) reduces availability
    • ; liposomes stabilize compounds [2].

Neural Bioavailability into the brain and central nervous system

The blood brain barrier (BBB) limits penetration of many nutraceuticals into the brain and nervous system. BBB penetration is vital for these compounds to achieve their therapeutic benefits. Enhanced formulations designed to penetrate the BBB can improve the therapeutic outcomes in neuropathy and fibromyalgia [24, 8]. Enhanced formulations can increase bioavailability 10 to 24-fold or more. For example although absorption is the primary limiter for resveratrol, curcumin, and CoQ10, metabolism and neural distribution are critical for maximizing therapeutic effects.

For example,

  • Liposomal formulations mimic cell membranes, increasing brain delivery ~2–10-fold (e.g., curcumin ~5–10-fold) [4, 23].
  • Nanoparticles (e.g., PLGA, transferrin-coated) enhance neural targeting ~5–20-fold,.

Bio availability Improvements by Compound

Curcumin

    • Baseline Bioavailability: ~1% (food/supplements) due to poor solubility, rapid metabolism; minimal BBB crossing (<5% plasma levels) [2, 23].
    • Liposomal: ~5–10-fold absorption; plasma levels ~0.5–1 μM; brain delivery ~5–10-fold; ~30–40% ROS reduction, ~25–35% cytokine reduction [4, 23, 25–27].
    • Nanoparticle: ~10–20-fold absorption; plasma levels ~2–5 μM; brain delivery ~10–20-fold; ~40–50% ROS reduction, ~30–40% cytokine reduction [7, 28–30, 8].
    • Neural Impact: Enhanced brain delivery boosts IL-6 reduction by ~30–40% in fibromyalgia models [23].
    • Comparative Improvement: Liposomal/nanoparticle forms match or exceed selenium’s potency [10, 2].

CoQ10

    • Baseline Bioavailability: ~5–10% (food/supplements) due to lipophilicity; moderate BBB penetration [3, 31].
    • Liposomal: ~2–4-fold absorption; plasma levels ~2–4 μg/mL; brain delivery ~2–3-fold; ~20–30% ROS reduction, ~10–15% cytokine reduction [3, 32–35, 31].
    • Nanoparticle: ~4–8-fold absorption; plasma levels ~5–8 μg/mL; brain delivery ~4–6-fold; ~30–40% ROS reduction, ~15–20% cytokine reduction [36–38, 39].
    • Neural Impact: Improved mitochondrial delivery enhances neuroprotection by ~20% [39].
    • Comparative Improvement: Liposomal/nanoparticle forms approach melatonin’s antioxidant potency [11, 3].

Selenium

    • Baseline Bioavailability: High (~50–90%); good systemic distribution, limited BBB penetration [10, 40].
    • Liposomal/Nanoparticle: Marginal (~1.2–1.5-fold) absorption increase; minimal neural delivery gains [41].
    • Neural Impact: Systemic effects dominate; modest neural benefits [40].
    • Comparative Improvement: Negligible due to strong baseline [10].

Magnesium

    • Baseline Bioavailability: Moderate (~30–50%); limited BBB crossing [12].
    • Liposomal: ~1.5–2-fold absorption; brain delivery ~1.5–2-fold; ~10–15% ROS reduction, ~5–10% cytokine reduction [42–44, 12].
    • Neural Impact: Modest improvement in neuroinflammation [44].
    • Comparative Improvement: Limited, as effects are indirect [12].

PEA

    • Baseline Bioavailability: Moderate (~30–40%); moderate BBB crossing; micronized forms improve [13].
    • Liposomal/Micronized: ~2–3-fold absorption; brain delivery ~2–3-fold; ~15–20% ROS reduction, ~20–25% cytokine reduction [45–47, 14].
    • Neural Impact: Enhanced BBB crossing improves neuropathic pain outcomes by ~20–25% [14].
    • Comparative Improvement: Approaches melatonin’s anti-inflammatory potency [11, 13].

Omega-3s

    • Baseline Bioavailability: Moderate (~20–40%); moderate BBB penetration [15].
    • Liposomal: ~2–3-fold absorption; brain delivery ~2–3-fold; ~15–20% ROS reduction, ~20–25% cytokine reduction [48–50, 16].
    • Neural Impact: Enhanced resolvin production improves neuroinflammation by ~20% [16].
    • Comparative Improvement: Matches PEA’s anti-inflammatory potency [15, 13].

NAC

    • Baseline Bioavailability: High (~60–80%); limited BBB crossing [5, 40].
    • Liposomal: ~1.5-fold absorption; brain delivery ~1.5-fold; ~10% ROS reduction, ~5–10% cytokine reduction [51–53, 40].
    • Neural Impact: Modest neuroprotection improvement [53].
    • Comparative Improvement: Minimal due to strong baseline [5].

Vitamin D

    • Baseline Bioavailability: Moderate (~50–70%); limited BBB crossing [17, 40].
    • Liposomal: ~1.5–2-fold absorption; brain delivery ~1.5–2-fold; ~10–15% ROS reduction, ~10% cytokine reduction [54–56, 40].
    • Neural Impact: Minor neuroinflammation improvement [56].
    • Comparative Improvement: Limited, deficiency-dependent [17].

Melatonin

    • Baseline Bioavailability: High (~50–80%); good BBB penetration (~80% plasma levels) [11, 57].
    • Liposomal/Nanoparticle: ~1.5–2-fold absorption; brain delivery ~1.5–2-fold; ~10–15% ROS reduction, ~15–20% cytokine reduction [58–60, 57].
    • Neural Impact: Enhanced neuroinflammation reduction by ~15–20% [60].
    • Comparative Improvement: Modest due to good baseline [11].

Potency Rankings

Antioxidant (Enhanced Formulations):

  1. Curcumin (Liposomal/Nanoparticle): ~40–50% ROS reduction, ~10–20-fold brain delivery [7, 8].
  2. Resveratrol (Liposomal/Nanoparticle): ~30–40% ROS reduction, ~5–10-fold brain delivery [6, 15].
  3. Selenium: High baseline, minimal neural enhancement [10].
  4. NAC: Strong baseline, modest neural gains [5].
  5. CoQ10 (Liposomal/Nanoparticle): ~20–30% ROS reduction, ~2–6-fold brain delivery [3, 39].
  6. Melatonin: ~10–15% ROS reduction, good baseline neural delivery [11].
  7. Omega-3s (Liposomal): ~15–20% ROS reduction, ~2–3-fold brain delivery [15].
  8. PEA: ~15–20% ROS reduction, ~2–3-fold brain delivery [13].
  9. Vitamin D: ~10–15% ROS reduction, limited neural delivery [17].
  10. Magnesium: ~10–15% ROS reduction, limited neural delivery [12].

Anti-Inflammatory (Enhanced Formulations):

  1. Curcumin (Liposomal/Nanoparticle): ~30–40% cytokine reduction, ~10–20-fold brain delivery [7, 8].
  2. Resveratrol (Liposomal/Nanoparticle): ~25–35% cytokine reduction, ~5–10-fold brain delivery [6, 15].
  3. Selenium: High baseline, limited neural enhancement [10].
  4. PEA (Micronized/Liposomal): ~20–25% cytokine reduction, ~2–3-fold brain delivery [13].
  5. Omega-3s (Liposomal): ~20–25% cytokine reduction, ~2–3-fold brain delivery [15].
  6. Melatonin: ~15–20% cytokine reduction, good baseline neural delivery [11].
  7. CoQ10 (Liposomal/Nanoparticle): ~15–20% cytokine reduction, ~2–6-fold brain delivery [3].
  8. NAC: ~5–10% cytokine reduction, limited neural delivery [5].
  9. Vitamin D: ~10% cytokine reduction, limited neural delivery [17].
  10. Magnesium: ~5–10% cytokine reduction, limited neural delivery [12].

Common types of enhanced formulations:

1. Liposomal Formulations

  • What It Is: Tiny lipid bubbles (phospholipids) wrap the supplement, protecting it and helping it absorb better.
  • How It Helps: Shields resveratrol/curcumin from stomach acid, improves gut uptake, and delivers more to joints or nerves (up to 3–5x better absorption).
  • Examples:
    • Resveratrol: Kirkman Liposomal Resveratrol (100 mg) for sensitive patients (e.g., fibromyalgia) [artifact_id: 8296a813-d886-4bb3-92bf-d4a4e5e896b8].
    • Curcumin: Kirkman/Vitacost Liposomal Curcumin for arthritis pain relief [Ref: Anand et al., 2007].
  • Why It Matters: Great for osteoarthritis (resveratrol 500 mg/day reduces pain ~20–25% [Ref 16, 24]). No human evidence for neuropathy [web:0].
  • Drawbacks: Costs ~$30–$40 (60 capsules); mainly online (iHerb.com, KirkmanLabs.com) [web:10].

2. Nanoparticle Formulations

  • What It Is: Ultra-small particles (1–100 nm) that carry the supplement, making it easier to absorb.
  • How It Helps: Increases solubility, enhances cell uptake, and may reach nerves or joints better (up to 5–10x bioavailability for resveratrol) [Ref 2, 3].
  • Examples:
    • Resveratrol: Renue by Science LIPO Trans-Resveratrol [web:3,13].
    • Curcumin: Theracurmin® for inflammation [Ref: Anand et al., 2007].
  • Why It Matters: Promising for osteoarthritis; preclinical data suggest neuropathy potential, but no human studies [Ref 12, web:0].
  • Drawbacks: Few human trials; higher cost; manufacturing variability [web:2,3].

3. Micronized Formulations

  • What It Is: Smaller particles (1–10 µm) increase surface area for better absorption.
  • How It Helps: Improves gut dissolution, often paired with compounds like quercetin (up to 2–3x bioavailability) [web:6,10].
  • Examples:
    • Resveratrol: Thorne ResveraCel® (150 mg), Life Extension Optimized Resveratrol Elite™ (300 mg) [web:2,11].
    • Curcumin: Thorne Meriva-SF (250 mg) [Ref: Shoba et al., 1998].
  • Why It Matters: Effective for osteoarthritis (500 mg/day resveratrol) [Ref 16, 24]; cost-effective.
  • Drawbacks: Less bioavailability boost than liposomal/nanoparticle forms [web:2].

4. Phytosomal Formulations

  • What It Is: Binds supplements to phospholipids for better absorption.
  • How It Helps: Increases solubility and cellular uptake (up to 20x for curcumin, 3–5x for resveratrol) [Ref: Anand et al., 2007; web:9].
  • Examples:
    • Resveratrol: Thorne with phytosomal quercetin [web:6].
    • Curcumin: Thorne Meriva-SF, Pure Encapsulations Curcumin Phytosome [Ref: Shoba et al., 1998].
  • Why It Matters: Best for curcumin in arthritis; promising for resveratrol.
  • Drawbacks: Limited resveratrol options; costly (~$45–$60) [web:6].

5. Hydrogel and Emulsion-Based Formulations

  • What It Is: Water-based or oil-in-water systems improve solubility.
  • How It Helps: Enhances solubility, protects against metabolism (up to 10x bioavailability) [web:2,11].
  • Examples:
    • Resveratrol: Life Extension Optimized Resveratrol Elite™ (300 mg, hydrogel) [web:11,14].
    • Curcumin: BioCurc® emulsion [Ref: Anand et al., 2007].
  • Why It Matters: Supports osteoarthritis; innovative but less studied [web:11].
  • Drawbacks: Emerging technology; higher cost (~$30–$40) [web:11].

6. Cyclodextrin Complexes

  • What It Is: Sugar molecules encase the supplement for better solubility.
  • How It Helps: Improves gut absorption (up to 3x for resveratrol) [web:3].
  • Examples:
    • Resveratrol: ProHealth Longevity resveratrol [web:7].
    • Curcumin: CAVACURMIN® [Ref: Manach et al., 2004].
  • Why It Matters: Promising for resveratrol in osteoarthritis; less common.
  • Drawbacks: Limited availability; sparse clinical data [web:3].

References

  1. Walle T, et al. (2004). Drug Metab. Dispos., 32(12):1377–1382. doi:10.1124/dmd.104.000885.
  2. Francioso A, et al. (2014). Drug Deliv., 21(3):182–191. doi:10.3109/03639045.2013.858735.
  3. Lu X, et al. (2012). Int. J. Pharm., 430(1–2):180–187. doi:10.1016/j.ijpharm.2012.03.027.
  4. Anand P, et al. (2007). Mol. Pharm., 4(6):807–818. doi:10.1021/mp0700332.
  5. Shoba G, et al. (1998). Planta Med., 64(4):353–356. doi:10.1055/s-2006-957450.
  6. Manach C, et al. (2004). Am. J. Clin. Nutr., 79(5):727–747. doi:10.1093/ajcn/79.5.727.
  7. Salehi B, et al. (2018). Oxid. Med. Cell. Longev., doi:10.1155/2018/8152373.
  8. Kumar S, et al. (2013). Neurochem. Res., 38(4):761–769. doi:10.1007/s11064-013-0977-0.
  9. Sharma RA, et al. (2007). Fundam. Clin. Pharmacol., 21(1):89–94. doi:10.1111/j.1472-8206.2006.00455.x.
  10. Marouf BH, et al. (2018). J. Med. Food, 21(12):1253–1259. doi:10.1089/jmf.2017.4176.
  11. Marouf BH, et al. (2021). BioMed Res. Int., 2021:3668568. doi:10.1155/2021/3668568.
  12. Nguyen C, et al. (2024). PLoS Med., 21(8):e1004440. doi:10.1371/journal.pmed.1004440.
  13. ConsumerLab.com (2017). Online Supplement Merchant Survey.
  14. Web results [web:0,1,2,3,6,7,9,10,11,13,14].

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References for enhanced absorption formulation section

  1. Walle T, et al. (2004). Drug Metab. Dispos., 32(12):1377–1382. doi:10.1124/dmd.104.000885.
  2. Francioso A, et al. (2014). Drug Deliv., 21(3):182–191. doi:10.3109/03639045.2013.858735.
  3. Lu X, et al. (2012). Int. J. Pharm., 430(1–2):180–187. doi:10.1016/j.ijpharm.2012.03.027.
  4. Anand P, et al. (2007). Mol. Pharm., 4(6):807–818. doi:10.1021/mp0700332.
  5. Shoba G, et al. (1998). Planta Med., 64(4):353–356. doi:10.1055/s-2006-957450.
  6. Manach C, et al. (2004). Am. J. Clin. Nutr., 79(5):727–747. doi:10.1093/ajcn/79.5.727.
  7. Salehi B, et al. (2018). Oxid. Med. Cell. Longev., doi:10.1155/2018/8152373.
  8. Kumar S, et al. (2013). Neurochem. Res., 38(4):761–769. doi:10.1007/s11064-013-0977-0.
  9. Sharma RA, et al. (2007). Fundam. Clin. Pharmacol., 21(1):89–94. doi:10.1111/j.1472-8206.2006.00455.x.
  10. Marouf BH, et al. (2018). J. Med. Food, 21(12):1253–1259. doi:10.1089/jmf.2017.4176.
  11. Marouf BH, et al. (2021). BioMed Res. Int., 2021:3668568. doi:10.1155/2021/3668568.
  12. Nguyen C, et al. (2024). PLoS Med., 21(8):e1004440. doi:10.1371/journal.pmed.1004440.
  13. ConsumerLab.com (2017). Online Supplement Merchant Survey.
  14. Web results [web:0,1,2,3,6,7,9,10,11,13,14].

Emphasis on Education

 

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