Nutraceuticals: 

Nutraceuticals for Central Sensitization (CS)

As a key player in the driving forces behind chronic pain, central sensitization (CS) should be a target in the management of any chronic pain syndrome, likely to be associated with CS. At this time, there is no specific conventional prescription management for CS. Rather, treatment of CS is generally directed at individual drivers of CS including system systemic inflammation, oxidative stress, and mitochondrial dysfunction. This section explores nutraceutical compounds, potentially be beneficial for the management of Central sensitization.

 

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Handout:  Nutraceuticals for Central Sensitization

 

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Definitions and Terms Related to Pain

 

Nutraceuticals for Central Sensitization

Compounds that have garnered interest in treating central sensitization include curcumin, palmitoylethanamide (PEA), acetyl L-carnitine (ALC), alpha lipoid acid (ALA), cannabidiol (CBD), delta-9 THC, acetyl cysteine (NAC) and low dose naltrexone (LDN). Additionally, various dietary compounds including Omega-3 and polyphenols, including resveratrol and catechins such as EGCG have also been proposed to reduce central sensation.

 

Summary:

Nutraceuticals for Central Sensitization

Central sensitization (CS) is when your nervous system becomes more sensitive to stimulation, especially pain but also to heat, cold or stress. It magnifies the sense of pain and makes it last longer. CS is common in many chronic pain conditions including neck or low back pain, arthritis (OA), nerve pain, fibromyalgia and migraines. It is a consequence of systemic inflammation and oxidative stress, the conditions that drive chronic pain. Reducing these processes is the ultimate goal of the anti-inflammatory diet as well as the recommended lifestyle changes for chronic pain. Use of these supplements may help reduce pain sensitivity now and in the future.

How These Supplements Work

Most of these compounds work by reducing inflammation and/or oxidation, protecting nerves from damage or calming overactive nerves. They are recommended to supplement a broader pain management plan which that includes exercise, an anti-inflammatory diet, stress management and mindful activities (e.g. meditation, prayer).

Safety

  • Always talk to your healthcare provider before starting any supplement as they may interact with other medicines
  • Buy supplements from reputable brands to ensure quality.
  • These compounds are generally safe and well tolerated but they may cause nausea or mild stomach upset.

Supplements for Central Sensitization

Alpha-Lipoic Acid (ALA)

  • What it is: An antioxidant found in foods like spinach and broccoli.
  • How it works: May help protect nerves and reduce inflammation.
  • Dosing: 600 mg per day.
  • Evidence: Shown to help with diabetic nerve pain, but not effective for all types of nerve pain or fibromyalgia.

Acetyl-L-Carnitine (ALC)

  • What it is: A nutrient that helps with energy production in cells.
  • How it works: May support nerve health and reduce pain signals.
  • Dosing: 500–1000 mg twice daily.
  • Evidence: May help with diabetic nerve pain, but not recommended for chemotherapy-related nerve pain.

Curcumin (from Turmeric)

  • What it is: The active ingredient in turmeric spice.
  • How it works: Powerful anti-inflammatory and may calm overactive nerve cells.
  • Dosing: 500–1000 mg per day (look for enhanced-absorption “bioavailable” forms).
  • Evidence: May help with pain in osteoarthritis and possibly fibromyalgia, but more research is needed.

Omega-3 Fatty Acids (Fish Oil)

  • What it is: Healthy fats found in fish and some plants.
  • How it works: Reduces inflammation in the body and nervous system.
  • Dosing: 1–3 grams per day of EPA/DHA.
  • Evidence: helps with osteoarthritis, migraine, headaches, peripheral neuropathy

N-Acetylcysteine (NAC)

  • What it is: An antioxidant supplement.
  • How it works: May reduce inflammation and protect nerve cells.
  • Dosing: 600–1200 mg per day.
  • Evidence: Early research suggests possible benefit for nerve pain

Boswellia (Indian Frankincense)

  • What it is: An herbal extract from the Boswellia serrata tree.
  • •How it works: Blocks inflammation and helps protect joint cartilage.
  • Dosing: 100–300 mg twice daily (standardized extract).
  • Evidence: Strong for reducing pain & stiffness in OA; benefits seen within 5–7 days, lasting up to 3 months.

Palmitoylethanolamide (PEA)

  • What it is: A fatty compound found in foods like egg yolks and peanuts.
  • How it works: May reduce inflammation and calm overactive nerve cells.
  • Dosing: 300–600 mg twice daily.
  • Evidence: Studies support benefit for nerve pain and fibromyalgia

Other Foods and Supplements

  • Green Tea. especially Matcha Green Tea (rich in anti-oxidants)
  • Unsweetened Cocoa Powder  (rich in anti-oxidants)
  • Vitamin D: (potent anti-inflammatory benefits)
  • Magnesium: (regulates nerve receptors and neurotransmitter activity)
  • Polyphenols (plant-based compounds like resveratrol reduce inflammation)

Low-Dose Naltrexone (LDN) –  Prescription Only

  • What it is: A medication used at low doses (1.5–4.5 mg/day) for fibromyalgia
  • Evidence: May be used with opioids to reduce opioid-induced hyperalgesia (OIH) and CS

Supplements by Medical Condition

Fibromyalgia

  • Supplements with likely benefit: Curcumin, low-dose naltrexone (LDN), palmitoylethanolamide (PEA), omega-3 fatty acids.
  • Evidence level: Moderate for LDN and curcumin; limited for PEA and omega-3s.

Diabetic Nerve Pain (Diabetic Peripheral Neuropathy)

  • Supplements with likely benefit: Alpha-lipoic acid (ALA), acetyl-L-carnitine (ALC), vitamin D.
  • Evidence level: Good for ALA and ALC; moderate for vitamin D.

Osteoarthritis

  • Supplements with likely benefit: Curcumin, omega-3 fatty acids.
  • Evidence level: Strong for Boswellia and omega-3s (reduces pain, stiffness, Moderate for curcumin

Chemotherapy-Induced Nerve Pain

  • Supplements with possible benefit: Limited evidence for N-acetylcysteine (NAC), magnesium, and vitamin E.
  • Evidence level: Early research; not enough data for strong recommendations.

Complex Regional Pain Syndrome (CRPS)

  • Supplements with possible benefit: Vitamin C (early use may help prevent CRPS after injury).
  • Evidence level: Early research; more studies needed.

Chronic Back Pain

  • Supplements with possible benefit: Curcumin, omega-3 fatty acids, magnesium.
  • Evidence level: Limited; more research needed.

Mechanistic Rationale for Adjunctive Supplements

Central sensitization, a key driver of chronic pain syndromes such as fibromyalgia, neuropathic pain, osteoarthritis, relapsing multiple sclerosis (MS), and inflammatory bowel diseases (IBD), is characterized by heightened excitability of central nervous system neurons, often perpetuated by neuroinflammation, oxidative stress, and glial activation.

Oral adjunctive supplements—including curcumin, palmitoylethanolamide (PEA), acetyl-L-carnitine (ALC), alpha-lipoic acid (ALA), cannabidiol (CBD), omega-3 fatty acids, resveratrol, and epigallocatechin gallate (EGCg)—have been shown in preclinical and, to a lesser extent, clinical studies to modulate these pathophysiological processes.

Curcumin, the principal polyphenol in turmeric, exerts its effects by suppressing microglial and astrocyte activation, reducing the expression of pro-inflammatory cytokines (e.g., IL-1β, TNF-α, IL-6), and enhancing antioxidant defenses such as superoxide dismutase (SOD1) and the Nrf2 pathway. In rodent models of neuropathic pain, oral curcumin and bisdemethoxycurcumin reduced mechanical hypersensitivity and glial activation in both the spinal cord and amygdala, while improving mitochondrial function and reducing TLR4-mediated neuroinflammation.[1-2] Polyphenols such as resveratrol and EGCg also target TLR4/NF-κB signaling, downregulating pro-inflammatory mediators and normalizing cytokine profiles in both peripheral and central tissues.[2-3]

PEA, an endogenous fatty acid amide, modulates neuroinflammation by downregulating mast cell and glial cell activation, thereby reducing the release of neurotoxic mediators and pro-inflammatory cytokines.[4]

ALC and ALA contribute to analgesia by enhancing mitochondrial function, reducing oxidative stress, and modulating neurotransmitter systems and neurotrophic factors, including nerve growth factor and metabotropic glutamate receptors.[5-6] CBD and other cannabinoids inhibit microglial activation and reduce neuroinflammation through downregulation of NADPH oxidase-mediated ROS production and suppression of TLR4-NFκB and IFN-β-JAK-STAT pathways.[7-8]

Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), exert anti-inflammatory and antinociceptive effects by reducing pro-inflammatory cytokines and upregulating anti-inflammatory IL-10.[9]

Collectively, these compounds converge on key mechanistic pathways—suppression of glial activation, inhibition of pro-inflammatory signaling, restoration of redox balance, improvement of mitochondrial function, and regulation of cytokine profiles—providing a strong rationale for their adjunctive use in chronic pain syndromes characterized by central sensitization.[1-6][8-9]

Comparative Clinical Efficacy and Safety by Condition

Fibromyalgia and Neuropathic Pain

The most robust clinical evidence for oral adjunctive supplements in fibromyalgia and neuropathic pain supports the use of PEA, ALC, and, to a lesser extent, curcumin and ALA.

PEA and ALC

In a randomized controlled trial of 130 fibromyalgia patients, the addition of PEA (600 mg twice daily) and ALC (500 mg twice daily) to stable duloxetine and pregabalin therapy over 12 weeks resulted in statistically significant improvements in the Widespread Pain Index, Fibromyalgia Impact Questionnaire, and Fibromyalgia Assessment Status scores compared to standard therapy alone (p = 0.048 for WPI, p = 0.033 for FIQR, p = 0.017 for FASmod).[10] No major adverse events were reported, supporting the safety of this combination.

ALA was not effective for fibromyalgia in a randomized, placebo-controlled, crossover trial.[16-17]

PEA

Meta-analyses of PEA in chronic pain, including nociplastic pain such as fibromyalgia, demonstrate significant reductions in pain scores at 4–26 weeks (SMD range: -0.36 to -1.16), with improvements in quality of life and no major side effects.[4][11-13] PEA was effective for nociceptive, neuropathic, and nociplastic pain, with a pooled standard mean difference of 1.68 (95% CI 1.05 to 2.31, p = 0.00001) for pain reduction compared to placebo or active comparators.[12]

Curcumin

Curcumin has been evaluated in both preclinical and clinical settings. A meta-analysis of 30 clinical studies found that oral curcumin (100–250 mg/day) and nano-curcumin formulations significantly reduced chronic pain, with effect sizes favoring enhanced bioavailability preparations (SMD for oral curcumin: 1.27, 95% CI 1.01 to 1.55, p < 0.001).[14]

Curcumin is well tolerated, with no significant safety concerns identified. However, human studies specifically in fibromyalgia remain limited and inconclusive, and narrative reviews highlight the need for more robust clinical trials.[15]

CBD has been investigated in a recent randomized, double-blind, placebo-controlled trial in fibromyalgia. At a dose of 50 mg daily for 24 weeks, CBD did not reduce pain compared to placebo; in fact, the placebo group had a greater reduction in pain scores (mean change: -0.4 points in CBD group vs -1.1 points in placebo group, between-group difference -0.7 points, 95% CI -1.2 to -0.25, p = 0.0028).[18] Adverse events were mild and evenly distributed between groups. (Dose too low?)

Diabetic Peripheral Neuropathy (DPN)

ALA and ALC are supported for use in diabetic peripheral neuropathy (DPN), with ALA at 600 mg/day and ALC at 500–1000 mg twice daily demonstrating moderate efficacy and good safety.[5-6][16] In contrast, ALC may be ineffective or harmful in chemotherapy-induced neuropathy.[16-17]

CBD has been investigated in a recent randomized, double-blind, placebo-controlled trial in fibromyalgia. At a dose of 50 mg daily for 24 weeks, CBD did not reduce pain compared to placebo; in fact, the placebo group had a greater reduction in pain scores (mean change: -0.4 points in CBD group vs -1.1 points in placebo group, between-group difference -0.7 points, 95% CI -1.2 to -0.25, p = 0.0028).[18] Adverse events were mild and evenly distributed between groups. (Dose too low?

Osteoarthritis

In osteoarthritis, curcumin and Boswellia have the strongest evidence for efficacy among oral supplements. A network meta-analysis of 39 RCTs (4599 patients) found that Boswellia showed significant improvements in WOMAC pain (mean difference [MD] = 10.58, 95% CI 6.45 to 14.78), stiffness (MD = 9.47, 95% CI 6.39 to 12.74), function (MD = 14.00, 95% CI 7.74 to 20.21), and VAS pain (MD = 17.26, 95% CI 8.06 to 26.52) compared to placebo.[19]

Curcumin, collagen, ginger, and krill oil also demonstrated benefits in some outcomes, with no supplement associated with increased adverse events compared to placebo. A systematic review and meta-analysis of 42 RCTs found that nutraceutical supplementation improved total WOMAC index (SMD = -0.23, 95% CI -0.37 to -0.08), WOMAC pain (SMD = -0.36, 95% CI -0.62 to -0.10), WOMAC stiffness (SMD = -0.47, 95% CI -0.71 to -0.23), and VAS pain (SMD = -0.79, 95% CI -1.05 to -0.05).[20] These improvements were more pronounced with longer supplementation durations.

Migraines

See:  CAM Treatment of Migraine Headaches

 

Multiple Sclerosis (relapsing)

For relapsing MS, the most comprehensive synthesis is provided by a 2020 Cochrane review, which found that supplementation with polyunsaturated fatty acids (PUFAs), antioxidants, and other natural health products did not demonstrate clear benefit over monounsaturated fatty acids or placebo in terms of relapse rate, disability progression, or global clinical status.[23]

Similarly, antioxidant supplementation—including curcumin, resveratrol, and EGCg—did not show significant effects on relapses, disability progression, or MRI outcomes compared to placebo, and the evidence remains insufficient to support clinical recommendations for these adjuncts in MS management.[23-25]

 

Inflammatory Bowel Disease (IBD)

In  IBD, reviews of complementary and alternative medicine agents—including cannabinoids, curcumin, resveratrol, and Boswellia—note that while some studies report positive outcomes and anti-inflammatory effects, the literature is limited by small sample sizes, lack of standardization, and absence of large-scale RCTs.[26]

There are currently no large-scale RCTs or real-world studies published that definitively establish the efficacy of these oral supplements as adjuncts in IBD.

Synergy and Multimodal Approaches

The rationale for combining oral adjunctive supplements with conventional pain medications is grounded in the multifactorial nature of central sensitization, which involves neuroinflammatory, oxidative, and neurotransmitter-mediated pathways. Preclinical and clinical data support the potential for synergy among certain combinations.

In fibromyalgia, the combination of PEA and ALC with duloxetine and pregabalin resulted in additional significant improvements in pain and functional outcomes compared to standard therapy alone, demonstrating clinically meaningful synergy.[10]

Marchesi et al. reviewed the pain-relieving effects of non-drug oral integrators and noted that combinations of B vitamins with gabapentin or diclofenac improved outcomes in chronic postoperative and neuropathic pain, and that ALA was effective in burning mouth syndrome.[27]

These observations suggest that adjunctive compounds may enhance the efficacy of conventional agents, potentially by modulating neuroinflammation, oxidative stress, and mitochondrial function.

Preclinical studies have demonstrated that combinations such as tramadol with topiramate, gabapentin, or lamotrigine produce synergistic attenuation of nerve injury-induced allodynia in animal models.[28] A co-crystal formulation of ketoprofen lysine salt and gabapentin resulted in enhanced anti-nociceptive and anti-inflammatory effects, as well as reduced spinal neuroinflammation, compared to either agent alone or their simple combination.[29]

Guidelines from the American Society of Anesthesiologists and the American Society of Regional Anesthesia and Pain Medicine advocate for multimodal pharmacologic strategies, including anticonvulsants, antidepressants, NSAIDs, and NMDA receptor antagonists, for neuropathic and chronic pain syndromes.[30]

While these guidelines do not specifically address nutraceuticals, they emphasize the importance of combining agents with different mechanisms of action to optimize pain control and minimize adverse effects.

 

Practical Recommendations: Efficacy, Dosing, and Affordability

The most clinically actionable recommendations for oral adjunctive supplements in chronic pain management are limited to curcumin and Boswellia for osteoarthritis, and ALA and ALC (for diabetic peripheral neuropathy only) for neuropathic pain, based on moderate evidence of efficacy, good safety, and affordability.

  • For osteoarthritis, curcumin is recommended at 100–250 mg/day, preferably as a nano-formulation to enhance bioavailability, with typical monthly costs of $10–$30.[14][31]
  • Boswellia is recommended at 300–500 mg/day, with similar cost and safety profiles.[19][31]
  • ALA is recommended for diabetic peripheral neuropathy at 600 mg/day
  • ALC at 500–1000 mg twice daily, with monthly costs of $15–$40.[5-6][16]
  • PEA is recommended at 600 mg twice daily for chronic pain, with micronized or ultramicronized formulations preferred for enhanced absorption.[4][10-13][32-33]

For other chronic pain conditions, including fibromyalgia, migraines, relapsing MS, and IBD, there is insufficient evidence to recommend any oral adjunctive supplement.

CBD and delta-9 THC

CBD and delta-9 THC are generally safe but lack consistent efficacy in fibromyalgia and other pain conditions, and are costly ($40–$100 per month for CBD, $200–$400 per month for prescription THC).[18][34]

Omega-3 fatty acids are recommended at 1–3 g/day (EPA+DHA), taken with food to maximize absorption, with monthly costs of $10–$40.[20][31][35-36]

Resveratrol and EGCg are generally safe at standard oral doses (resveratrol 100–500 mg/day, EGCg 200–400 mg/day), but clinical efficacy data are insufficient to support their use in chronic pain management.[27]

A summary table from Liu et al published in Rheumatology (Oxford, England) provides a concise comparison of the efficacy, safety, and cost-effectiveness of these supplements for osteoarthritis, highlighting curcumin and Boswellia as the most effective and affordable options.[31]

Curcumin

  • Typical Monthly Cost: $10–$30
  • Evidence for Efficacy (Pain Reduction): Moderate to large (OA, short-term)
  • Safety Profile: Good
  • Cost-Effectiveness: High
  • Synergy Potential with Boswellia, NSAIDs
  • References:[1-3]

Boswellia

  • Typical Monthly Cost: $10–$30
  • Evidence for Efficacy (Pain Reduction):  Large (OA, pain/stiffness)
  • Safety Profile: Good
  • Cost-Effectiveness: High
  • Synergy Potential with curcumin, NSAIDs
  • References:[1-2, 4]

Collagen

  • Typical Monthly Cost: $20–$40
  • Evidence for Efficacy (Pain Reduction):  Moderate (OA, short-term)
  • Safety Profile: Good
  • Cost-Effectiveness: Moderate
  • Synergy Potential with other supplements
  • References:[1-2]

Krill oil

  • Typical Monthly Cost: $20–$40
  • Evidence for Efficacy (Pain Reduction):  Moderate (OA, function)
  • Safety Profile: Good
  • Cost-Effectiveness: Moderate
  • Synergy Potential with omega-3s
  • References:[2]

Ginger

  • Typical Monthly Cost: <$10
  • Evidence for Efficacy (Pain Reduction):  Modest (OA)
  • Safety Profile: Good
  • Cost-Effectiveness: High
  • Synergy Potential with curcumin
  • References:[2]

ALA (Alpha Lipoic Acid)

  • Typical Monthly Cost: $15–$30
  • Evidence for Efficacy (Pain Reduction):  Moderate (neuropathic pain)
  • Safety Profile: Good
  • Cost-Effectiveness: Moderate
  • Synergy Potential with ALC, gabapentin
  • References:[5]

ALC (Acetyl-L-carnitine)

  • Typical Monthly Cost: $20–$40
  • Evidence for Efficacy (Pain Reduction):  Moderate (neuropathic pain)
  • Safety Profile: Good
  • Cost-Effectiveness: Moderate
  • Synergy Potential with ALA, B vitamins
  • References:[1, 5]

CBD (Cannabidiol)

  • Typical Monthly Cost: $40–$100
  • Evidence for Efficacy (Pain Reduction):   Inconsistent (MS, neuropathic pain)
  • Safety Profile: Good
  • Cost-Effectiveness: Low–Moderate
  • Synergy Potential with THC, other supplements
  • References:[4, 6]

THC (Tetrahydracannabidiol)

  • Typical Monthly Cost: $200–$400
  • Evidence for Efficacy (Pain Reduction):  Inconsistent (MS, neuropathic pain)
  • Safety Profile: Moderate
  • Cost-Effectiveness: Low
  • References: [6]

 

Safety, Interactions, and Special Populations

The safety profile of oral supplements commonly used as adjuncts in chronic pain management is generally favorable, with a low risk of clinically significant adverse interactions when combined with conventional pain medications.

Most pain-focused nutraceuticals, including curcumin, ALA, ALC, omega-3s, and NAC, do not exhibit significant pharmacokinetic or pharmacodynamic interactions with standard analgesics at typical oral doses.[39-47] Cannabinoids require more careful consideration due to their effects on cytochrome P450 enzymes and potential for CNS depression, especially when combined with other sedatives or opioids.[44]

Incidence

Large cross-sectional studies and systematic reviews indicate that the actual incidence of serious harm from supplement-drug interactions in clinical practice is low. In a survey of nearly 1,800 patients, the majority of clinically significant interactions involved a small number of supplements (garlic, valerian, kava, ginkgo, St. John’s wort) and a small number of drug classes (antithrombotics, sedatives, antidepressants, antidiabetics), with no serious harm reported.[40] The most serious interactions typically involve agents with narrow therapeutic indices or chronic, high-dose use of both the supplement and the interacting drug.[45-46]

Risk

Older adults, individuals with multiple comorbidities, and those experiencing polypharmacy are at increased risk for adverse effects and reduced efficacy when using oral supplements adjunctively. The prevalence of concurrent use of prescription drugs and dietary supplements in community-dwelling populations aged 50 years and older ranges from approximately 14% to over 30%.[48-51]

The risk of potential major drug-supplement interactions increases with age, with 4.5% of concurrent drug-supplement users in a large Irish cohort identified as being at risk for major interactions.[49]

Emergency department visits for supplement-related adverse events are most commonly associated with micronutrients (iron, calcium, potassium) in adults aged 65 years or older, and with herbal or complementary nutritional products in younger adults.[52]

A visual summary of emergency department visits for adverse events associated with dietary supplements, according to age group and product category, is provided in Figure 2 from Geller et al published in The New England Journal of Medicine.[52] This figure highlights the increased risk of adverse events in older adults, particularly with micronutrient supplements.

Figure 2. National Estimates of Emergency Department Visits for Adverse Events Associated with Dietary Supplements, According to Age Group and Product Category (2004–2013).

Emergency Department Visits for Adverse Events Related to Dietary Supplements. N Engl J Med. October 14, 2015.

Used under license from The New England Journal of Medicine.

Long-term safety and tolerability of chronic oral supplementation with curcumin, PEA, ALC, ALA, CBD, delta-9 THC, NAC, LDN, omega-3, resveratrol, and EGCg are generally favorable when used at standard oral doses and for durations up to six months, with most reported side effects being mild and transient.[4-6][11-14][32-33][53-55]

Serious adverse events are rare, but the absence of multi-year data means that rare or cumulative toxicities cannot be entirely excluded, and ongoing monitoring is warranted in clinical practice.

Conclusion

In summary, the most robust evidence for adjunctive oral treatment of central sensitization in chronic pain syndromes supports the use of curcumin and Boswellia for osteoarthritis, and ALA and ALC (for diabetic peripheral neuropathy only) for neuropathic pain.

These agents are well tolerated, affordable, and have favorable safety profiles. PEA shows promise in fibromyalgia and neuropathic pain, with significant reductions in pain and improvements in quality of life, but high-quality randomized controlled trials are limited.

CBD and cannabinoids are generally safe but lack consistent efficacy in fibromyalgia and other pain conditions, and are costly.

For other chronic pain conditions, including fibromyalgia, migraines, relapsing MS, and IBD, there is insufficient evidence to recommend any oral adjunctive supplement. The key evidence gaps include the lack of high-quality, controlled trials for most supplements, insufficient data on long-term safety and cost-effectiveness, and a need for studies evaluating synergistic effects with conventional medications.

Patients should prioritize supplements with the strongest evidence for efficacy, safety, and affordability, and remain vigilant for potential drug-supplement interactions, particularly in older adults and those with polypharmacy.  Routine medication reconciliation should include specific questions about dietary supplement use, and decisions regarding adjunctive supplementation should be individualized based on patient preferences, clinical context, and the current evidence base.

Ongoing research is needed to clarify the role of these oral adjuncts in chronic pain management, particularly in conditions such as MS and IBD where evidence is currently lacking.

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19. 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.

20. 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.

21. 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.

22. Nonnarcotic Methods of Pain Management. Finnerup NB. The New England Journal of Medicine. 2019;380(25):2440-2448. doi:10.1056/NEJMra1807061.

23. Dietary Interventions for Multiple Sclerosis-Related Outcomes. Parks NE, Jackson-Tarlton CS, Vacchi L, Merdad R, Johnston BC. The Cochrane Database of Systematic Reviews. 2020;5:CD004192. doi:10.1002/14651858.CD004192.pub4.

24. Use of Vitamins and Dietary Supplements by Patients With Multiple Sclerosis: A Review. Evans E, Piccio L, Cross AH. JAMA Neurology. 2018;75(8):1013-1021. doi:10.1001/jamaneurol.2018.0611.

25. Effects of Anti-Inflammatory-Antioxidant-Rich Diet and Co-Supplemented Synbiotics Intervention in Patients With Progressive Forms of Multiple Sclerosis: A Single-Center, Single-Blind Randomized Clinical Trial. Moravejolahkami AR, Chitsaz A, Hassanzadeh A, Paknahad Z. Nutritional Neuroscience. 2023;26(11):1078-1089. doi:10.1080/1028415X.2022.2128010.

26. Selected Use of Complementary and Alternative Medicine (CAM) Agents in IBD. Dzwonkowski M, Bahirwani J, Rollins S, et al. Current Gastroenterology Reports. 2025;27(1):1. doi:10.1007/s11894-025-00960-0.

27. 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.

28. Tramadol and Several Anticonvulsants Synergize in Attenuating Nerve Injury-Induced Allodynia. Codd EE, Martinez RP, Molino L, et al. Pain. 2008;134(3):254-262. doi:10.1016/j.pain.2007.04.019.

29. Ketoprofen, Lysine and Gabapentin Co-Crystal Magnifies Synergistic Efficacy and Tolerability of the Constituent Drugs: Pre-Clinical Evidences Towards an Innovative Therapeutic Approach for Neuroinflammatory Pain. Aramini A, Bianchini G, Lillini S, et al. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2023;163:114845. doi:10.1016/j.biopha.2023.114845.

30. Practice Guidelines for Chronic Pain Management: An Updated Report by the American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2010;112(4):810-33. doi:10.1097/ALN.0b013e3181c43103. Practice Guideline

31. Which Supplements Can I Recommend to My Osteoarthritis Patients?. Liu X, Eyles J, McLachlan AJ, Mobasheri A. Rheumatology (Oxford, England). 2018;57(suppl_4):iv75-iv87. doi:10.1093/rheumatology/key005.

32. 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.

33. 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.

34. Cannabis and Cannabidiol (CBD) for the Treatment of Fibromyalgia. Berger AA, Keefe J, Winnick A, et al. Best Practice & Research. Clinical Anaesthesiology. 2020;34(3):617-631. doi:10.1016/j.bpa.2020.08.010.

35. 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.

36. Early Evidence of Efficacy for Orally Administered SPM-enriched Marine Lipid Fraction on Quality of Life and Pain in A sample of Adults With Chronic Pain. Callan N, Hanes D, Bradley R. Journal of Translational Medicine. 2020;18(1):401. doi:10.1186/s12967-020-02569-5.

37. Promising Health Benefits of Adjuvant and Extracts Combined With Coenzyme Q10 Phytosomes, Supplementation in Chronic Pain Treated With Medical Cannabis: A Prospective and Open-Label Clinical Study. Poli P, Carnevale S, Scocca A, et al. Evidence-Based Complementary and Alternative Medicine : eCAM. 2022;2022:7099161. doi:10.1155/2022/7099161.

38. CDC Clinical Practice Guideline for Prescribing Opioids for Pain – United States, 2022. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. MMWR. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports. 2022;71(3):1-95. doi:10.15585/mmwr.rr7103a1. Practice Guideline

39. Common Herbal Dietary Supplement-Drug Interactions. Asher GN, Corbett AH, Hawke RL. American Family Physician. 2017;96(2):101-107.

40. Potential for Interactions Between Dietary Supplements and Prescription Medications. Sood A, Sood R, Brinker FJ, et al. The American Journal of Medicine. 2008;121(3):207-11. doi:10.1016/j.amjmed.2007.11.014.

41. Pharmacokinetic Assessment of Constituents of Boswellia Serrata, Pine Bark Extracts, Curcumin in Combination Including Methylsulfonylmethane in Healthy Volunteers. Liu X, Hunter DJ, Eyles J, et al. The Journal of Pharmacy and Pharmacology. 2020;72(1):121-131. doi:10.1111/jphp.13184.

42. Herbal Medication: Potential for Adverse Interactions With Analgesic Drugs. Abebe W. Journal of Clinical Pharmacy and Therapeutics. 2002;27(6):391-401. doi:10.1046/j.1365-2710.2002.00444.x.

43. Pharmacokinetic and Pharmacodynamic Herb-Drug Interactions of Common Over-the-Counter Pain Medications. Sun CK, Tsai TH. Biomedical Chromatography : BMC. 2023;37(7):e5591. doi:10.1002/bmc.5591.

44. Herbal Medicine for Pain Management: Efficacy and Drug Interactions. Jahromi B, Pirvulescu I, Candido KD, Knezevic NN. Pharmaceutics. 2021;13(2):251. doi:10.3390/pharmaceutics13020251.

45. Adverse Drug Interactions Involving Common Prescription and Over-the-Counter Analgesic Agents. Hersh EV, Pinto A, Moore PA. Clinical Therapeutics. 2007;29 Suppl:2477-97. doi:10.1016/j.clinthera.2007.12.003.

46. Adverse Drug Reactions and Drug-Drug Interactions With Over-the-Counter NSAIDs. Moore N, Pollack C, Butkerait P. Therapeutics and Clinical Risk Management. 2015;11:1061-75. doi:10.2147/TCRM.S79135.

47. Preoperative Management of Surgical Patients Using Dietary Supplements: Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement. Cummings KC, Keshock M, Ganesh R, et al. Mayo Clinic Proceedings. 2021;96(5):1342-1355. doi:10.1016/j.mayocp.2020.08.016. Practice Guideline

48. Prevalence of Drug-Herb and Drug-Supplement Interactions in Older Adults: A Cross-Sectional Survey. Agbabiaka TB, Spencer NH, Khanom S, Goodman C. The British Journal of General Practice : The Journal of the Royal College of General Practitioners. 2018;68(675):e711-e717. doi:10.3399/bjgp18X699101.

49. Concurrent Use of Drugs and Supplements in a Community-Dwelling Population Aged 50 Years or More: Potential Benefits and Risks. Peklar J, Henman MC, Kos M, Richardson K, Kenny RA. Drugs & Aging. 2014;31(7):527-40. doi:10.1007/s40266-014-0180-6.

50. Prevalence of Medication-Dietary Supplement Combined Use and Associated Factors. Aznar-Lou I, Carbonell-Duacastella C, Rodriguez A, Mera I, Rubio-Valera M. Nutrients. 2019;11(10):E2466. doi:10.3390/nu11102466.

51. Analysis of Oral Dietary Supplement Use in Rural Older Adults. Shade MY, Witry M, Robinson K, Kupzyk K. Journal of Clinical Nursing. 2019;28(9-10):1600-1606. doi:10.1111/jocn.14763.

52. Emergency Department Visits for Adverse Events Related to Dietary Supplements. Geller AI, Shehab N, Weidle NJ, et al. The New England Journal of Medicine. 2015;373(16):1531-40. doi:10.1056/NEJMsa1504267.

53. Analgesic Efficacy and Safety of Curcuminoids in Clinical Practice: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sahebkar A, Henrotin Y. Pain Medicine (Malden, Mass.). 2016;17(6):1192-202. doi:10.1093/pm/pnv024.

54. Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Panknin TM, Howe CL, Hauer M, et al. International Journal of Molecular Sciences. 2023;24(5):4476. doi:10.3390/ijms24054476.

55. Reprint Of: Efficacy, Tolerability, and Safety of Non-Pharmacological Therapies for Chronic Pain: An Umbrella Review on Various CAM Approaches. Houzé B, El-Khatib H, Arbour C. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2018;87(Pt B):307-321. doi:10.1016/j.pnpbp.2018.08.002.

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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