Nutraceuticals: 

Nutraceutical Combinations & Synergies

Many nutraceuticals can be more effective when taken in combination with other nutraceuticals (or other medications and treatments). This section focuses mostly on combining nutraceuticals. Combining nutraceuticals can have an additive effect (1+1 = 2) or a synergy effect, in which the combination of compounds enhances the benefits of the individual compounds to be greater than the sum of the parts, such that  1+1 = 3, known as “synergy.”

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Definitions and Terms Related to Pain

 

Nutraceutical Combinations & Synergies

POTENTIAL OPIOID-SPARING SYNERGY COMBINATIONS:

1. Melatonin + Sulforaphane + Taurine: All 3 interact with opioid systems through different mechanisms:

    1. Melatonin: MT2 → vlPAG → PENK → MOR recruitment
    2. Sulforaphane: Restores MOR expression
    3. Taurine: Attenuates morphine tolerance

2. Curcumin + Melatonin:

    1. Curcumin activates peripheral opioid receptors
    2. Melatonin recruits endogenous opioid pathways centrally

GENERAL RECOMMENDATIONS:

  • Curcumin + Boswellia + Omega-3: Complementary anti-inflammatory mechanisms (COX-2 + 5-LOX + prostaglandin modulation) for osteoarthritis and inflammatory pain[1][2][7]
  • Alpha-Lipoic Acid + Acetyl-L-Carnitine: Synergistic neuroprotection and mitochondrial support for diabetic neuropathy[9][8]
  • PEA + Curcumin: Endocannabinoid modulation plus anti-inflammatory effects for neuropathic and chronic pain[10][11]
  • Vitamin D + Magnesium: Vitamin D requires magnesium for activation; combined benefits for musculoskeletal pain[6][7]

GENERAL RECOMMENDATIONS BY PAIN TYPE:

   Osteoarthritis:

  • Omega-3 (2-3 gm EPA+DHA/day)
  • First-line: Curcumin (enhanced bioavailability, 500-1000 mg/day) + Boswellia (100-400 mg standardized extract/day)
  • Add: PEA (ultramicronized, 600 mg BID) [1][2][7]
  • Add:: Resveratrol (250-500 mg/day)
  • Add: Quercetin (500-1000 mg/day)
  • Consider: Glucosamine/Chondroitin (consider for OA if structural concerns)[1][2][14]

   Neuropathic Pain:

  • First-line: Alpha-lipoic acid (600 mg/day) + Acetyl-L-carnitine (2000-3000 mg/day)
  • Add: PEA (ultramicronized, 600 mg BID) + Omega-3 (1-1.35 g EPA+DHA/day)
  • Consider: Quercetin [9][8][10][11] >
  • Consider: NAD+ precursors (NR 500 mg/day)
  • Consider:  Taurine (1500-3000 mg/day)

   Inflammatory Pain:

  • Omega-3 (2-3 gm EPA+DHA/day)
  • First-line: Curcumin (enhanced bioavailability, 500-1000 mg/day) + Boswellia (100-400 mg standardized extract/day)
  • Add: PEA (ultramicronized, 600 mg BID) [1][2][7]
  • Add:: Resveratrol (250-500 mg/day)
  • Add: Quercetin (500-1000 mg/day)

   Fibromyalgia/Central Sensitization:

  • First-line: PEA (ultramicronized, 600 mg BID) + CoQ10 (300 mg/day) + Vitamin D (if deficient)
  • Add: Magnesium (400-600 mg/day) + Melatonin (3-5 mg at bedtime) [6][10][11]
  • Consider: SAMe
  • Consider: Omega-3,

   Migraine Prophylaxis:

  • Omega-3 (2-3 gm EPA+DHA/day)
  • First-line: Magnesium (400-600 mg/day) + CoQ10 (300 mg/day)
  • Add:  Melatonin (3 mg at bedtime)
  • Consider: Riboflavin (B2, 400 mg/day)

   Chemotherapy-Induced Neuropathy:

  • First-line: Alpha-lipoic acid (600-1200 mg/day) + Acetyl-L-carnitine ??  (2000-3000 mg/day)
  • Add: NAD+ precursors (NR 500-1000 mg/day)
  • Consider: PEA, Omega-3

   

    References

  1. A Meta-Analysis of the Impact of Nutritional Supplementation on Osteoarthritis Symptoms. Mathieu S, Soubrier M, Peirs C, et al. Nutrients. 2022;14(8):1607. doi:10.3390/nu14081607.
  2. Comparative Effectiveness of Nutritional Supplements in the Treatment of Knee Osteoarthritis: A Network Meta-Analysis. Zhang Y, Gui Y, Adams R, et al. Nutrients. 2025;17(15):2547. doi:10.3390/nu17152547.
  3. The Non-Surgical Management of Hip & Knee Osteoarthritis (OA) (2020). Matthew Bair MD MS, John Cody MD, Jess Edison MD, et al. Department of Veterans Affairs.
  4. The Analgesic Effect of Curcumin and Nano-Curcumin in Clinical and Preclinical Studies: A Systematic Review and Meta-Analysis. Hajimirzaei P, Eyni H, Razmgir M, et al. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2025;398(1):393-416. doi:10.1007/s00210-024-03369-0.
  5. Effects of Omega-3 Fatty Acids on Chronic Pain: A Systematic Review and Meta-Analysis. Xie L, Wang X, Chu J, et al. Frontiers in Medicine. 2025;12:1654661. doi:10.3389/fmed.2025.1654661.
  6. The Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Pain Prevalence and Severity in Older Adults: A Large-Scale Ancillary Study of the VITamin D and OmegA-3 triaL (VITAL). Soens MA, Sesso HD, Manson JE, et al. Pain. 2024;165(3):635-643. doi:10.1097/j.pain.0000000000003044.
  7. New Concepts of Chronic Pain and the Potential Role of Complementary Therapies. Wojcikowski K, Vigar VJ, Oliver CJ. Alternative Therapies in Health and Medicine. 2020;26(S1):18-31.
  8. The Role of Diet and Non-Pharmacologic Supplements in the Treatment of Chronic Neuropathic Pain: A Systematic Review. Frediani JK, Lal AA, Kim E, et al. Pain Practice : The Official Journal of World Institute of Pain. 2024;24(1):186-210. doi:10.1111/papr.13291.
  9. Non-Drug Pain Relievers Active on Non-Opioid Pain Mechanisms. Marchesi N, Govoni S, Allegri M. Pain Practice : The Official Journal of World Institute of Pain. 2022;22(2):255-275. doi:10.1111/papr.13073.
  10. Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding. Viña I, López-Moreno M. Nutrition Reviews. 2025;83(7):e1604-e1618. doi:10.1093/nutrit/nuae203.
  11. Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Lang-Illievich K, Klivinyi C, Lasser C, et al. Nutrients. 2023;15(6):1350. doi:10.3390/nu15061350.
  12. Evidence-Based Evaluation of Complementary Health Approaches for Pain Management in the United States. Nahin RL, Boineau R, Khalsa PS, Stussman BJ, Weber WJ. Mayo Clinic Proceedings. 2016;91(9):1292-306. doi:10.1016/j.mayocp.2016.06.007.
  13. Nutraceutical Supplements in Management of Pain and Disability in Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Aghamohammadi D, Dolatkhah N, Bakhtiari F, Eslamian F, Hashemian M. Scientific Reports. 2020;10(1):20892. doi:10.1038/s41598-020-78075-x.
  14. Dietary Supplements for Treating Osteoarthritis: A Systematic Review and Meta-Analysis. Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. British Journal of Sports Medicine. 2018;52(3):167-175. doi:10.1136/bjsports-2016-097333.
  15. A Standardized Boswellia Serrata Extract Shows Improvements in Knee Osteoarthritis Within Five Days-a Double-Blind, Randomized, Three-Arm, Parallel-Group, Multi-Center, Placebo-Controlled Trial. Majeed A, Majeed S, Satish G, et al. Frontiers in Pharmacology. 2024;15:1428440. doi:10.3389/fphar.2024.1428440.
  16. Oral Herbal Therapies for Treating Osteoarthritis. Cameron M, Chrubasik S. The Cochrane Database of Systematic Reviews. 2014;(5):CD002947. doi:10.1002/14651858.CD002947.pub2.

 

SYNERGY COMBINATIONS

   Within Pain Processing Category:

1. B-Complex Vitamins + Gabapentin: Effective for CIPN and neuropathic pain; B vitamins enhance gabapentin efficacy[11]

2. B-Complex + Diclofenac: Effective for low back pain; combination allows lower NSAID doses[11]

3. PEA + Hemp Oil Extract: Preclinical evidence shows synergistic anti-nociceptive effects—sub-effective doses of each produce greater-than-additive pain relief; HOE enhances and prolongs systemic PEA exposure[12]

4. Magnesium + Taurine: Complementary inhibitory neurotransmission (NMDA block + glycinergic activation)—theoretical synergy based on non-overlapping mechanisms

5. ALA + ALC: Complementary neuroprotection (antioxidant + nerve regeneration); both target diabetic neuropathy through different pathways

   Within Tissue Modification Category:

1. Boswellia + Celery Seed Extract: 2025 RCT showed combination (300 mg Boswellia + 250 mg celery) reduced inflammatory markers and cartilage degeneration biomarkers while increasing collagen synthesis markers (PIIANP, PIICP)[13]

2. Omega-3 + Sulforaphane: Complementary chondroprotection (SPM generation + Nrf2 activation)—theoretical synergy

3. Omega-3 + Vitamin D3: Both address tissue inflammation; vitamin D may enhance omega-3 incorporation into cell membranes

   Across Categories: Pain Processing +Tissue Modification:

1. PEA + β-Caryophyllene + Carnosic Acid + Myrrh: Preclinical study showed this combination (Noxiall®) produced efficacy comparable to gabapentin/pregabalin for neuropathic pain; co-administration of sub-effective doses of pregabalin + Noxiall produced additive efficacy[14]

2. Curcumin + Omega-3: Dual anti-inflammatory pathways; curcumin provides acute pain relief through opioid/cannabinoid receptor activation while omega-3 addresses tissue inflammation through SPM generation

3. Curcumin + Quercetin: Both have dual mechanisms; quercetin adds senolytic effect for disease modification; both require bioavailability-enhanced formulations

4. PEA + Curcumin: PEA for central/peripheral sensitization + curcumin for tissue protection and peripheral opioid/cannabinoid activation

 

   References

  1. Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Lang-Illievich K, Klivinyi C, Lasser C, et al. Nutrients. 2023;15(6):1350. doi:10.3390/nu15061350.
  2. Extended Treatment With Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis. Schweiger V, Schievano C, Martini A, et al. Nutrients. 2024;16(11):1653. doi:10.3390/nu16111653.
  3. Ultramicronized N-Palmitoylethanolamine Associated With Analgesics: Effects Against Persistent Pain. Nobili S, Micheli L, Lucarini E, et al. Pharmacology & Therapeutics. 2024;258:108649. doi:10.1016/j.pharmthera.2024.108649.
  4. Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding. Viña I, López-Moreno M. Nutrition Reviews. 2025;83(7):e1604-e1618. doi:10.1093/nutrit/nuae203.
  5. Neuropsychopharmacological Actions of Taurine. Banerjee SP, Ragnauth A, Chan CY, et al. Advances in Experimental Medicine and Biology. 2013;775:3-18. doi:10.1007/978-1-4614-6130-2_1.
  6. Randomised Clinical Trial: Oral Taurine Supplementation Versus Placebo Reduces Muscle Cramps in Patients With Chronic Liver Disease. Vidot H, Cvejic E, Carey S, et al. Alimentary Pharmacology & Therapeutics. 2018;48(7):704-712. doi:10.1111/apt.14950.
  7. Antinociceptive Effect of Intrathecal Administration of Taurine in Rat Models of Neuropathic Pain. Terada T, Hara K, Haranishi Y, Sata T. Canadian Journal of Anaesthesia = Journal Canadien d’Anesthesie. 2011;58(7):630-637. doi:10.1007/s12630-011-9504-8.
  8. Comparative Investigation of Analgesic Tolerance to Taurine, Sodium Salicylate and Morphine: Involvement of Peripheral Muscarinic Receptors. Akbari E, Beheshti F, Zarmehri HA, et al. Neuroscience Letters. 2023;795:137041. doi:10.1016/j.neulet.2022.137041.
  9. Taurine Enhances Antinociception Produced by a COX-2 Inhibitor in an Inflammatory Pain Model. de Rienzo-Madero B, Coffeen U, Simón-Arceo K, et al. Inflammation. 2013;36(3):658-64. doi:10.1007/s10753-012-9589-4.
  10. A Phase II, Randomized, Double-Blind, Placebo Controlled, Dose-Response Trial of the Melatonin Effect on the Pain Threshold of Healthy Subjects. Stefani LC, Muller S, Torres IL, et al. PloS One. 2013;8(10):e74107. doi:10.1371/journal.pone.0074107.
  11. Analgesic Efficacy of Melatonin: A Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials. Oh SN, Myung SK, Jho HJ. Journal of Clinical Medicine. 2020;9(5):E1553. doi:10.3390/jcm9051553.
  12. Melatonin for Neuropathic Pain: A Double-Blind, Placebo-Controlled, Randomized, Crossover Trial. Gilron I, Elkerdawy H, Tu D, et al. Pain. 2025;:00006396-990000000-00905. doi:10.1097/j.pain.0000000000003651.
  13. Magnesium and Pain. Shin HJ, Na HS, Do SH. Nutrients. 2020;12(8):E2184. doi:10.3390/nu12082184.
  14. A Double-Blinded Randomised Controlled Study of the Value of Sequential Intravenous and Oral Magnesium Therapy in Patients With Chronic Low Back Pain With a Neuropathic Component. Yousef AA, Al-deeb AE. Anaesthesia. 2013;68(3):260-6. doi:10.1111/anae.12107.

 

Synergistic Combination Recommendations by Mechanistic Category

Synergy Category

Nutraceutical

Combinations

Mechanistic Rationale

Clinical Application

Reference

s

Mitochondrial

Support Stack

CoQ10 + NR +

ALC + Taurine

CoQ10 (electron transport) +

NR (NAD⁺ provision) + ALC

(fatty acid delivery) +

Taurine (mt-protein

synthesis)

Fibromyalgia, chronic

fatigue with pain,

aging-related pain

[1], [2],

[3], [4]

Nrf2 Activation

Stack

Sulforaphane +

Curcumin +

Resveratrol +

ALA

Convergent Nrf2 activation

through complementary

mechanisms; ALA recycles

other antioxidants

Neuropathic pain,

chemotherapy-induced

neuropathy

[1], [5],

[6], [7]

Neuroinflammation

Stack

PEA + Omega-3

+ Melatonin +

Curcumin

PEA (PPAR-α) + Omega-3

(SPMs) + Melatonin

(NLRP3) + Curcumin (NF-

κB) for multi-target

microglial modulation

Central sensitization,

chronic widespread

pain

[1], [5],

[8], [9],

[10]

Glutathione

Support Stack

NAC + ALA +

Taurine

NAC (cysteine provision) +

ALA (GSH recycling) +

Taurine (GSH maintenance)

Oxidative stress-driven

pain, toxic

neuropathies

[1], [4],

[6], [11]

NMDA/

Excitotoxicity

Stack

Magnesium +

NAC + Taurine

Magnesium (NMDA block) +

NAC (glutamate modulation)

+ Taurine (glycine receptor

agonism)

Central sensitization,

wind-up, opioid

tolerance

[1], [4],

[11], [12]

Diabetic

Neuropathy Stack

ALA + ALC +

Magnesium +

Taurine +

Vitamin D3

Multi-target approach:

oxidative stress, nerve

regeneration, ion channels,

calcium signaling

Diabetic peripheral

neuropathy

[1], [4],

[6], [12],

[13], [14]

Anti-Inflammatory

Stack

Curcumin +

Boswellia +

Omega-3 +

Quercetin

COX/LOX inhibition + 5-

LOX inhibition + SPM

production + mast cell

stabilization

OA, RA, inflammatory

pain conditions

[1], [5],

[8], [15],

[16]

Sirtuin/NAD⁺ Axis

Stack

NR + Resveratrol

+ Quercetin

NR (NAD⁺ substrate) +

Resveratrol (SIRT1

activation) + Quercetin

(senolytic)

Aging-related chronic

pain, inflammaging

[1], [3],

[16], [17]

Migraine

Prevention Stack

CoQ10 +

Magnesium +

Melatonin +

Omega-3

Mitochondrial support +

NMDA modulation +

circadian regulation + anti-

inflammatory

Migraine prophylaxis

[1], [2],

[8], [10],

[12]

Spinal Cord

Modulation Stack

Magnesium +

Taurine + PEA +

Melatonin

NMDA antagonism + GlyR/

GABA-A agonism + glial

modulation + astrocyte

regulation

Central sensitization,

spinal cord injury pain

[1], [4],

[9], [10],

[12]

—

   References

  1. Quercetin Reprograms Immunometabolism of Macrophages via the SIRT1/PGC-1α Signaling Pathway to Ameliorate Lipopolysaccharide-Induced Oxidative Damage. Peng J, Yang Z, Li H, et al. International Journal of Molecular Sciences. 2023;24(6):5542. doi:10.3390/ijms24065542.
  2. Quercetin Preserves Redox Status and Stimulates Mitochondrial Function in Metabolically-Stressed HepG2 Cells. Houghton MJ, Kerimi A, Tumova S, Boyle JP, Williamson G. Free Radical Biology & Medicine. 2018;129:296-309. doi:10.1016/j.freeradbiomed.2018.09.037.
  3. Quercetin Increases Mitochondrial Biogenesis and Reduces Free Radicals in Neuronal SH-SY5Y Cells. Ho CL, Kao NJ, Lin CI, Cross TL, Lin SH. Nutrients. 2022;14(16):3310. doi:10.3390/nu14163310.
  4. Quercetin Induces Mitochondrial Biogenesis Through Activation of HO-1 in HepG2 Cells. Rayamajhi N, Kim SK, Go H, et al. Oxidative Medicine and Cellular Longevity. 2013;2013:154279. doi:10.1155/2013/154279.
  5. Quercetin and the Mitochondria: A Mechanistic View. de Oliveira MR, Nabavi SM, Braidy N, et al. Biotechnology Advances. 2016 Sep-Oct;34(5):532-549. doi:10.1016/j.biotechadv.2015.12.014.
  6. Protective Effects of Quercetin on Mitochondrial Biogenesis in Experimental Traumatic Brain Injury via the Nrf2 Signaling Pathway. Li X, Wang H, Gao Y, et al. PloS One. 2016;11(10):e0164237. doi:10.1371/ journal.pone.0164237.
  7. Quercetin Hinders Microglial Activation to Alleviate Neurotoxicity via the Interplay Between NLRP3 Inflammasome and Mitophagy. Han X, Xu T, Fang Q, et al. Redox Biology. 2021;44:102010. doi:10.1016/j.redox.2021.102010.
  8. Quercetin Ameliorates CFA-Induced Chronic Inflammatory Hyperalgesia via Modulation of ROS- Mediated ERK1/2 Signaling and Inhibition of Spinal Glial Activation in Vivo. Kumar S, Vinayak M. Neuromolecular Medicine. 2020;22(4):517-533. doi:10.1007/s12017-020-08609-z.
  9. Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice. Borghi SM, Pinho-Ribeiro FA, Fattori V, et al. PloS One. 2016;11(9):e0162267. doi:10.1371/journal.pone.0162267.
  10. Quercetin Alleviates Thermal and Cold Hyperalgesia in a Rat Neuropathic Pain Model by Inhibiting Toll-Like Receptor Signaling. Ji C, Xu Y, Han F, et al. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2017;94:652-658. doi:10.1016/j.biopha.2017.07.145.
  11. Quercetin Reduces Inflammation in a Rat Model of Diabetic Peripheral Neuropathy by Regulating the TLR4/MyD88/NF-κB Signalling Pathway. Zhao B, Zhang Q, Liang X, Xie J, Sun Q. European Journal of Pharmacology. 2021;912:174607. doi:10.1016/j.ejphar.2021.174607.
  12. Quercetin Relieved Diabetic Neuropathic Pain by Inhibiting Upregulated P2X Receptor in Dorsal Root Ganglia. Yang R, Li L, Yuan H, et al. Journal of Cellular Physiology. 2019;234(3):2756-2764. doi:10.1002/jcp.27091.
  13. Quercetin Attenuates Diabetic Neuropathic Pain by Inhibiting mTOR/p70S6K Pathway-Mediated Changes of Synaptic Morphology and Synaptic Protein Levels in Spinal Dorsal Horn of Db/Db Mice. Wang R, Qiu Z, Wang G, et al. European Journal of Pharmacology. 2020;882:173266. doi:10.1016/ j.ejphar.2020.173266.
  14. Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel. Liu Z, Shan Z, Yang H, et al. Anesthesia and Analgesia. 2024;138(6):1324-1336. doi:10.1213/ANE.0000000000006730.
  15. Quercetin Alleviates Osteoarthritis Pain by Inhibiting Vascular Endothelial Growth Factor a Through Regulating cGAS/STING Pathway. Hu E, Wei Y, Liao T, et al. Journal of Cellular and Molecular Medicine. 2026;30(1):e70992. doi:10.1111/jcmm.70992.
  16. Phytochemical Quercetin Alleviates Hyperexcitability of Trigeminal Nociceptive Neurons Associated With Inflammatory Hyperalgesia Comparable to NSAIDs. Itou H, Toyota R, Takeda M. Molecular Pain. 2022;18:17448069221108971. doi:10.1177/17448069221108971.
  17. The Effect of Quercetin on Inflammatory Factors and Clinical Symptoms in Women With Rheumatoid Arthritis: A Double-Blind, Randomized Controlled Trial. Javadi F, Ahmadzadeh A, Eghtesadi S, et al. Journal of the American College of Nutrition. 2017;36(1):9-15. doi:10.1080/07315724.2016.1140093.

 

Clinical Pearls for Combination Therapy:

   Highly Synergistic Combinations:

  • Curcumin + Boswellia + Omega-3: Complementary anti-inflammatory mechanisms (COX-2 + 5-LOX + prostaglandin modulation) for osteoarthritis and inflammatory pain[1][2][7]
  • Alpha-Lipoic Acid + Acetyl-L-Carnitine: Synergistic neuroprotection and mitochondrial support for diabetic neuropathy[9][8]
  • PEA + Curcumin: Endocannabinoid modulation plus anti-inflammatory effects for neuropathic and chronic pain[10][11]
  • Vitamin D + Magnesium: Vitamin D requires magnesium for activation; combined benefits for musculoskeletal pain[6][7]

   General Recommendations by Pain Type:

  • Osteoarthritis: Boswellia (1st line) > Curcumin > SAMe > PEA > Glucosamine/Chondroitin (consider if structural concerns)[1][2][14]
  • Neuropathic Pain: Alpha-Lipoic Acid (diabetic) > PEA > Acetyl-L-Carnitine > Quercetin[9][8][10][11]
  • Inflammatory Pain: Curcumin + Boswellia combination > Omega-3 > PEA[1][2][7]
  • Fibromyalgia: PEA > SAMe > Vitamin D (if deficient) > Magnesium[6][10][11]

References

  1. A Meta-Analysis of the Impact of Nutritional Supplementation on Osteoarthritis Symptoms. Mathieu S, Soubrier M, Peirs C, et al. Nutrients. 2022;14(8):1607. doi:10.3390/nu14081607.
  2. Comparative Effectiveness of Nutritional Supplements in the Treatment of Knee Osteoarthritis: A Network Meta-Analysis. Zhang Y, Gui Y, Adams R, et al. Nutrients. 2025;17(15):2547. doi:10.3390/nu17152547.
  3. The Non-Surgical Management of Hip & Knee Osteoarthritis (OA) (2020). Matthew Bair MD MS, John Cody MD, Jess Edison MD, et al. Department of Veterans Affairs.
  4. The Analgesic Effect of Curcumin and Nano-Curcumin in Clinical and Preclinical Studies: A Systematic Review and Meta-Analysis. Hajimirzaei P, Eyni H, Razmgir M, et al. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2025;398(1):393-416. doi:10.1007/s00210-024-03369-0.
  5. Effects of Omega-3 Fatty Acids on Chronic Pain: A Systematic Review and Meta-Analysis. Xie L, Wang X, Chu J, et al. Frontiers in Medicine. 2025;12:1654661. doi:10.3389/fmed.2025.1654661.
  6. The Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Pain Prevalence and Severity in Older Adults: A Large-Scale Ancillary Study of the VITamin D and OmegA-3 triaL (VITAL). Soens MA, Sesso HD, Manson JE, et al. Pain. 2024;165(3):635-643. doi:10.1097/j.pain.0000000000003044.
  7. New Concepts of Chronic Pain and the Potential Role of Complementary Therapies. Wojcikowski K, Vigar VJ, Oliver CJ. Alternative Therapies in Health and Medicine. 2020;26(S1):18-31.
  8. The Role of Diet and Non-Pharmacologic Supplements in the Treatment of Chronic Neuropathic Pain: A Systematic Review. Frediani JK, Lal AA, Kim E, et al. Pain Practice : The Official Journal of World Institute of Pain. 2024;24(1):186-210. doi:10.1111/papr.13291.
  9. Non-Drug Pain Relievers Active on Non-Opioid Pain Mechanisms. Marchesi N, Govoni S, Allegri M. Pain Practice : The Official Journal of World Institute of Pain. 2022;22(2):255-275. doi:10.1111/papr.13073.
  10. Meta-Analysis of Palmitoylethanolamide in Pain Management: Addressing Literature Gaps and Enhancing Understanding. Viña I, López-Moreno M. Nutrition Reviews. 2025;83(7):e1604-e1618. doi:10.1093/nutrit/nuae203.
  11. Palmitoylethanolamide in the Treatment of Chronic Pain: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials. Lang-Illievich K, Klivinyi C, Lasser C, et al. Nutrients. 2023;15(6):1350. doi:10.3390/nu15061350.
  12. Evidence-Based Evaluation of Complementary Health Approaches for Pain Management in the United States. Nahin RL, Boineau R, Khalsa PS, Stussman BJ, Weber WJ. Mayo Clinic Proceedings. 2016;91(9):1292-306. doi:10.1016/j.mayocp.2016.06.007.
  13. Nutraceutical Supplements in Management of Pain and Disability in Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Aghamohammadi D, Dolatkhah N, Bakhtiari F, Eslamian F, Hashemian M. Scientific Reports. 2020;10(1):20892. doi:10.1038/s41598-020-78075-x.
  14. Dietary Supplements for Treating Osteoarthritis: A Systematic Review and Meta-Analysis. Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. British Journal of Sports Medicine. 2018;52(3):167-175. doi:10.1136/bjsports-2016-097333.
  15. A Standardized Boswellia Serrata Extract Shows Improvements in Knee Osteoarthritis Within Five Days-a Double-Blind, Randomized, Three-Arm, Parallel-Group, Multi-Center, Placebo-Controlled Trial. Majeed A, Majeed S, Satish G, et al. Frontiers in Pharmacology. 2024;15:1428440. doi:10.3389/fphar.2024.1428440.
  16. Oral Herbal Therapies for Treating Osteoarthritis. Cameron M, Chrubasik S. The Cochrane Database of Systematic Reviews. 2014;(5):CD002947. doi:10.1002/14651858.CD002947.pub2.

Nutraceuticals with potentially higher impact based on pathophysiology:

  • Neuroinflammation → Curcumin, PEA, Sulforaphane
  • Oxidative stress → Alpha-lipoic acid, NAC, Resveratrol
  • Mitochondrial dysfunction → CoQ10, NAD+ precursors, Alpha-lipoic acid
  • Central sensitization → PEA, Omega-3, Magnesium

Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

 

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

 

For more information, please contact Accurate Clinic.

 

Supplements recommended by Dr. Ehlenberger may be purchased commercially online

Please read about our statement regarding the sale of products recommended by Dr. Ehlenberger.

 

 

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