Curcuma longa (Turmeric)

Nutriceuticals:

Curcumin

 Curcumin is the orange pigment in turmeric (a primary ingredient in curry).  It is a potent antioxidant and NRF2 activator that offers numerous health benefits, including supporting healthy joints, liver, the GI and cardiovascular system, and it helps to maintain the body’s normal inIammatory response.

 

A thorough review of curcumin is forthcoming but In the meantime, please review the section below regarding a recommended curcumin product, Meriva. At the bottom of this page there are links to many journal publications that explore the multiple potential benefits of curcumin.

The level of confidence (LOC) in most recommendation of curcumin as a supplement is high. 

See:

Nutraceuticals

 

See also:

Key to Links:

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  • Red text – another page on this website
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Definitions and Terms Related to Pain

 

Curcumin 

1. Introductory Summary

Curcumin, the active compound in turmeric (Curcuma longa), is a polyphenol with anti-inflammatory and antioxidant properties, making it useful in pain management for conditions, including  osteoarthritis and neuropathic pain as well as co-morbidities including cognitive function, fatigue, gut health, metabolic health, cardiovascular health, anxiety, depression, insomnia, and Alzheimer’s disease [1–7, 33–35]. Derived from the turmeric plant, native to Southeast Asia, curcumin has been used in Ayurvedic medicine for centuries to reduce inflammation, protect cells, and support overall wellness.

Curcumin is recommended for its ability to reduce systemic inflammation and oxidative stress, key drivers of pain amplification and chronic disease. Dietary sources, such as fresh turmeric root (20–180 mg curcumin/100 g) or curry powder (10–50 mg/100 g), provide low doses that are insufficient for therapeutic effects, so supplements (500–2000 mg/day) with enhanced formulations are essential to achieve meaningful benefits [8].

Curcumin is generally safe, with mild gastrointestinal upset at high doses (>4 g/day), but consult your doctor if taking blood thinners, diabetes medications, or for long-term use, as it may interact with certain drugs [9]. This treatise explores curcumin’s therapeutic roles, synergies, dosing, and mechanisms of action.

2. Understanding Systemic Inflammation and Oxidative Stress

“Systemic Inflammation” and “Oxidative Stress” are two conditions that contribute to chronic pain by creating a cycle of tissue damage, immune cell activation, and pain amplification. By disrupting normal cellular physiology, these conditions also contribute to the development and progression of chronic diseases, including diabetes, heart disease, stroke,, chronic kidney and liver disease, rheumatoid arthritis, cancer and Alzheimer’s [8].

  • Systemic inflammation is a widespread inflammatory response throughout the body, triggered by infection, injury, stress, or other conditions. It involves the release of pro-inflammatory molecules and activation of the immune system, contributing to chronic pain and leading to various health issues. Symptoms can include increased pain, fatigue, cognitive problems, depression, decreased physical activity, and, in severe cases, organ dysfunction. While inflammation is a natural part of the healing process, chronic or excessive systemic inflammation can contribute to the development of diseases like heart disease, diabetes, and autoimmune disorders [7].

    Neuroinflammation, a component of systemic inflammation, is inflammation within the central nervous system (brain and spinal cord). Systemic inflammation leads to the release of inflammatory molecules that cross the blood-brain barrier and activate immune cells in the brain, leading to or exacerbating, neuroinflammation.

    Neuroinflammation contributes to the progression of acute to chronic pain. It is characterized by activation of immune cells (glial cells and astrocytes) in the nervous system that release various inflammatory chemicals like cytokines, proteases, reactive oxygen (ROS), and nitrogen species (RNS). When these immune cells remain activated, neuroinflammation persists and drives chronic pain.

     

  • Oxidative stress is an imbalance in the body of excessive “oxidants” (oxidizing or chemically active agents, including free radicals, obtained from the diet or produced by the body) and insufficient “antioxidants” that neutralize oxidants (chemically active agents also obtained from the diet or produced by the body). Oxidative stress and chronic systemic inflammation coexist because they mutually induce each other. Oxidative stress, caused by excessive free radicals and insufficient antioxidant defenses, damages cells and tissues, including nerve cells, which leads to pain. Furthermore, this damage also triggers more inflammation, further exacerbating pain.

3. Supplements and the Anti-Inflammatory Diet

The anti-inflammatory diet emphasized at Accurate Clinic focuses on foods that help reduce inflammation and oxidative stress, potentially reducing chronic pain and the risk of chronic diseases. It emphasizes whole, unprocessed foods like fruits, vegetables, and healthy fats, while limiting or avoiding processed foods, red meat, and sugary drinks [9].

Although the anti-inflammatory diet is certainly of critical importance, even this healthy diet will not provide the level of anti-inflammatory and antioxidant nutrients that offer therapeutic benefits for the many common conditions that plague patients with chronic pain. For this reason, patients are encouraged to consider supplementing various nutrients to gain the benefits that the higher amounts will provide.

However, as is common with many nutraceutical supplements, the bioavailability of compounds may be severely limited in the absence of a formulation designed to enhance absorption and penetration into the brain and nervous system in order to gain their full benefits. As such, it is of value to understand the nature of enhanced formulations when considering the purchase of a nutraceutical product.

4. Curcumin’s Therapeutic Roles in:

Systemic Inflammation and Oxidative Stress

4a. Systemic Inflammation

Systemic inflammation is a widespread inflammatory response that can be triggered by various factors, including infections, injuries, or chronic conditions like obesity or autoimmune disorders. Curcumin, the active compound in turmeric, has been extensively studied for its potent anti-inflammatory properties. It works by inhibiting key pathways involved in inflammation, such as NF-κB and COX-2, which are responsible for the production of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α. These cytokines are released by immune cells and contribute to tissue damage and pain in conditions like osteoarthritis and rheumatoid arthritis.

In clinical trials, curcumin has shown significant reductions in markers of systemic inflammation, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). For example, in patients with metabolic syndrome, curcumin supplementation at 1 g/day for 8 weeks reduced CRP levels by approximately 30%, indicating a substantial decrease in systemic inflammation. Similarly, in rheumatoid arthritis patients, curcumin (500 mg/day) combined with diclofenac sodium was more effective than diclofenac alone in reducing disease activity scores, suggesting a synergistic effect. The mechanism involves curcumin’s ability to modulate the immune response, preventing excessive cytokine production that leads to chronic inflammation.

Curcumin’s anti-inflammatory effects extend to gut health, where it helps in conditions like Crohn’s disease and ulcerative colitis by reducing mucosal inflammation. A randomized trial showed that curcumin (3 g/day) maintained remission in ulcerative colitis patients better than placebo. For cardiovascular health, curcumin lowers inflammation in vascular endothelium, reducing the risk of atherosclerosis. Studies indicate that curcumin (500 mg/day) for 12 weeks improved endothelial function and reduced oxidative stress in healthy individuals.

Overall, curcumin’s role in systemic inflammation is supported by its multi-targeted approach, making it a promising supplement for chronic pain patients. However, bioavailability issues necessitate enhanced formulations like liposomal or nanoparticle curcumin to achieve therapeutic levels. Preclinical studies suggest benefits for neuropathy by reducing NF-κB in glial cells, but human data are limited. Curcumin ranks among leading anti-inflammatory nutraceuticals, with moderate confidence for systemic inflammation in osteoarthritis and gut health, low for neuropathy.

4b. Oxidative Stress

Oxidative stress occurs when there’s an imbalance between reactive oxygen species (ROS) and the body’s antioxidants, leading to cell damage. Curcumin acts as a powerful antioxidant by scavenging ROS and upregulating antioxidant enzymes like SOD, glutathione, and catalase through the Nrf2 pathway. In osteoarthritis, oxidative stress damages cartilage, and curcumin (500 mg/day, 8 weeks) has been shown to reduce ROS levels in synovial fluid, improving joint function and pain scores by ~20–30%.

For metabolic health, oxidative stress contributes to insulin resistance, and curcumin (1 g/day, 8 weeks) lowers oxidative markers like malondialdehyde (MDA) by ~25% in diabetic patients, enhancing insulin sensitivity. In cardiovascular health, curcumin reduces oxidized LDL, preventing atherosclerosis. Preclinical studies indicate curcumin’s potential in neuropathy, where ROS damage nerves; curcumin reduces ROS in diabetic models, but human trials are limited.

Curcumin’s antioxidant effects also support cognitive health by reducing amyloid-β plaques in Alzheimer’s models. Enhanced formulations like nanoparticle curcumin increase bioavailability, allowing lower doses to achieve similar effects. Overall, curcumin’s role in oxidative stress is well-supported for osteoarthritis and metabolic conditions, with high potency in reducing ROS and enhancing antioxidant defenses.

5. Summary list of  Curcumin’s therapeutic roles in:

Conditions with Moderate – High levels of Confidence (in scientific evidence)

  • Osteoarthritis: High confidence; reduces pain and inflammation (~20–30% WOMAC score improvement, RCTs).
  • Rheumatoid Arthritis: Moderate confidence; decreases disease activity (RCTs).
  • Crohn’s Disease/Ulcerative Colitis: High confidence; improves remission rates (RCTs).
  • Gut Health: High confidence; supports gut barrier and reduces IBS/IBD symptoms (RCTs).
  • Metabolic Health: High confidence; improves insulin sensitivity (~10–20% glucose reduction, RCTs).
  • Cardiovascular Health: Moderate confidence; lowers LDL and blood pressure (~10–15% reduction, RCTs).
  • Cognitive Function: Moderate confidence; enhances memory and reduces amyloid-β (RCTs).
  • Depression: Moderate confidence; improves mood (~20% HAM-D reduction, RCTs).
  • Systemic Inflammation: High confidence; lowers CRP and IL-6 (~10–20% reduction, RCTs).
  • Oxidative Stress: High confidence; reduces ROS and boosts antioxidants (RCTs).

6. Detailed information of Curcumin’s Therapeutic Roles in:

Pain and Pain-Related Conditions 

6a. Pain Conditions

Inflammatory Conditions

Overall, curcumin’s anti-inflammatory effects make it a promising adjunct therapy, with high confidence in gut and joint conditions, though bioavailability enhancements (e.g., piperine) are crucial for efficacy.Curcumin offers significant therapeutic potential in inflammatory conditions such as osteoarthritis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis.;

In osteoarthritis, curcumin modulates inflammatory pathways, reducing pain, stiffness, and joint swelling. RCTs demonstrate that doses of 500–1500 mg/day over 8–12 weeks lead to ~20–30% improvement in WOMAC scores (a questionnaire used to assess pain, stiffness, and physical function in individuals with osteoarthritis, particularly of the knee and hip), comparable to NSAIDs but with fewer side effects.

Evidence: High confidence – reduces pain and inflammation (~20–30% WOMAC score improvement, RCTs).

Mechanism: involves inhibiting NF-κB and COX-2, decreasing cytokine production (IL-1β, IL-6, TNF-α) in synovial cells, and protecting cartilage from degradation.

In rheumatoid arthritis, curcumin (1000 mg/day) reduces disease activity scores (DAS-28) by ~20–40% in RCTs, suppressing autoimmunity and joint destruction.

Evidence: Moderate confidence – decreases disease activity (RCTs).

Mechanisms: involves inhibiting NF-κB and COX-2, decreasing cytokine production (IL-1β, IL-6, TNF-α) in synovial cells, and protecting cartilage from degradation.

In Crohn’s disease, curcumin (1000–2000 mg/day) promotes mucosal healing with RCTs showing ~30% improvement in CDAI scores.

Evidence: High confidence – improves remission rates (RCTs).

Mechanism: Lowers TNF-α in intestinal cells,

In ulcerative colitis,

Evidence: High confidence – curcumin (2000 mg/day) enhances remission rates (~50% in RCTs), devastating improved endoscopic findings and symptoms like abdominal pain. Overall, curcumin’s anti-inflammatory effects make it a promising adjunct therapy, with high confidence in gut and joint conditions, though bioavailability enhancements (e.g., piperine) are crucial for efficacy.

Neuropathic Pain Conditions

Curcumin shows promise in neuropathic pain conditions, though evidence is mostly preclinical (laboratory  and animal studies) with limited human trials. Overall, curcumin’s role in neuropathic pain is supported by preclinical data, with moderate confidence for diabetic neuropathy and low for others, warranting enhanced formulations for better neural delivery.

In diabetic neuropathy (DPN), curcumin reduces nerve pain by downregulating inflammatory pathways in neurons and glial cells.

Animal studies in rats (200 mg/kg/day) demonstrate ~30–50% reduction in mechanical allodynia and thermal hyperalgesia.

Human studies A human pilot study (500–1000 mg/day, 8 weeks) report modest pain relief (~15–25% VAS reduction) in diabetic patients, improving nerve conduction velocity. Another small human trial (500 mg/day, 6 weeks) noted ~20% improvement in neuropathy symptoms, but larger RCTs are needed.For chemotherapy-induced neuropathy, curcumin protects peripheral nerves from oxidative damage. Oxidative stress and inflammation are the two major factors that contribute to the pathophysiology of diabetes and its complications. Curcumin reduces oxidative stress in DPN by increasing the key enzymes for antioxidant defense, such as SOD, and by increasing total antioxidant capacity (TAS) that provides protection from the neurological damage caused by diabetes-induced oxidative stress

Mechanism: mechanical allodynia and thermal hyperalgesia reduced by inhibiting HMGB1-TLR4-NF-κB signaling, lowering TNF-α and IL-6 in spinal cord tissues. Animal models (50–200 mg/kg/day) show curcumin attenuates paclitaxel-induced pain by inhibiting TLR4 and reducing ROS in dorsal root ganglia, preventing sensory deficits.

Mechanism: Curcumin is considered a potential treatment for diabetic neuropathy (DN) because it measurably reduces markers of oxidative stress and inflammatory cytokines, while significantly alleviating neuropathic pain and improving nerve function. Another mechanism by which curcumin impacts neuropathic pain is through interaction with MicroRNAs (miRNAs or miR) that regulate multiple target genes associated with neuropathy. Curcumin can regulate the dysregulation of relevant miRNAs by suppressing the inflammatory miRNAs while enhancing the anti-inflammatory miRNAs.

In Chemotherapy-Induced Peripheral Neuropathy (CIPN),

Preclinical studies Curcumin exerted higher efficacy in decreasing oxidative stress markers and increasing the endogenous antioxidative enzymes compared to standard drugs, including pregabalin (Lyruca).

Mechanims: In summary, the antinociceptive activity of curcumin against CIPN could be attributed to its multiple actions, including attenuating pain behaviors and increasing nerve conduction velocity and suppressing inflammatory proteins and cytokines.

In Sciatica, curcumin (300 mg/day, 2 weeks) reduced radicular pain in a pilot study (n=20), potentially by modulating TRPV1 channels in nerve roots, lowering pain scores ~25%.

In post-stroke pain and spinal cord injury nerve pain, curcumin has demonstrated potential benefits in combination with other compounds (see Synergies below with NACVAN® [containing NAC (300 mg), Curcuma longa extract (211 mg), Boswellia serrata extract (200 mg), and vitamins B1(10 mg), B6 (5 mg), and B12 (2.5 mcg)] administered with concurrent dosing of either gabapentin or pregabalin.

In Multiple Sclerosis, curcumin’s neuroprotective effects include reducing demyelination in preclinical EAE models by inhibiting IL-17 and enhancing myelin repair in oligodendrocytes. Early human trials (500 mg/day, 6 months) suggest reduced fatigue and pain (~15% EDSS improvement), but evidence is low.

In Migraine Headaches, Curcumin’s therapeutic role in migraine headaches is emerging but limited to small trials and preclinical data.

Animal studies (100 mg/kg) demonstrate curcumin attenuates nitroglycerin-induced migraines by lowering oxidative stress in brain tissues, improving blood-brain barrier integrity.

Human studies A pilot RCT (n=72, 500 mg/day curcumin + omega-3s, 2 months) showed ~30% reduction in migraine frequency and severity, potentially by modulating CGRP release in trigeminal ganglia.However, stand alone curcumin trials are scarce, with most evidence from combinations. Curcumin’s bioavailability issues limit efficacy; enhanced forms (e.g., nanoparticle) may improve brain delivery.

Evidence: Low confidence due to small samples and lack of large RCTs; further studies needed for dose optimization.

Mechanims: Migraines involve neurovascular inflammation, where curcumin inhibits COX-2 and NF-κB in vascular endothelial cells and trigeminal nerves, reducing prostaglandin E2 and cytokine release that triggers attacks.

In Dental and Oral Facial Region (OFR) pain – In summary, a 2022 systematic review of pertinent literature evaluated 19 RCTs assessing curcumin for post-dental extraction, pain, post-gum flap, surgery, pain, and other sources of oral pain. Results from 79% of the studies showed that curcumin exhibits analgesic properties and is effective in reducing self-rated pain in the OFR. These studies evaluated both topically applied curcumin gel as well as orally ingested curcumin, and both appear to offer pain benefits. This suggests that curcumin is a potent alternative herbal substitute for traditional pharmacological medications for the management of pain in the OFR. However, further research is needed to confirm this conclusion as there were some flaws noted in the systematic review.

6b. Pain-Related Conditions

 1. Peripheral and Central Sensitization

Curcumin addresses peripheral and central sensitization, mechanisms amplifying chronic pain. Peripheral sensitization occurs in nociceptors (pain receptors), where curcumin inhibits TRPV1 channels in sensory neurons, reducing hypersensitivity to heat and chemicals. Central sensitization involves spinal cord and brain changes; curcumin modulates NMDA receptors in dorsal horn neurons, lowering glutamate excitotoxicity.

Preclinical studies in rats (200 mg/kg/day) show curcumin reduces mechanical allodynia in neuropathic models by downregulating BDNF in spinal glial cells, preventing sensitization.

Human studies data are indirect, with RCTs in osteoarthritis (500 mg/day) suggesting reduced pain hypersensitivity via NF-κB inhibition in synovial tissues.

Evidence: Low confidence; more human trials needed.

2. Opioid Analgesic Tolerance

Curcumin may mitigate opioid analgesic tolerance, the reduced efficacy of pain medications like opioids over time. Tolerance involves mu-opioid receptor downregulation in neurons; curcumin enhances receptor sensitivity by inhibiting PKC in spinal cord, preventing desensitization. Animal rat models (200 mg/kg/day) show curcumin delays morphine tolerance, maintaining pain relief by reducing NF-κB in dorsal root ganglia. Human data are limited; a pilot study (500 mg/day) with NSAIDs in osteoarthritis suggested sustained efficacy, but no direct tolerance trials exist. Low confidence; preclinical promise warrants human studies.

3. Transition of Acute to Chronic Pain Acute postoperative treatment with curcumin has demonstrated anti-hyperalgesic activity by reversing mechanical hyperalgesia, and repeated treatment facilitated the recovery of postoperative pain . However, repeated treatment before surgery did not exert impact on the prevention or reduction in postoperative pain. The results emphasize that acute curcumin treatment may be useful in treating postoperative pain.

Curcumin may prevent the transition from acute to chronic pain by interrupting inflammatory cascades. Acute pain transitions to chronic via persistent NF-κB activation in immune and nerve cells, leading to central sensitization. Curcumin inhibits this in preclinical models, reducing IL-6 and TNF-α in spinal cord after injury. Rat studies (100 mg/kg/day) show curcumin attenuates post-surgical pain chronicity by lowering ROS in dorsal root ganglia, preventing nerve remodeling. No human RCTs directly address transition, but osteoarthritis trials (500 mg/day) suggest reduced chronic inflammation. Low confidence; preclinical data indicate potential.

6c. Other Conditions

  1. Cognitive Function/Enhancement Curcumin supports cognitive function by reducing oxidative stress and inflammation in brain cells. In healthy adults, RCTs (90–500 mg/day, 18 months) show improved memory and attention via reduced amyloid-β in hippocampus, enhancing BDNF in neurons. Curcumin’s Nrf2 activation in glial cells protects against ROS, improving executive function in aging populations. Moderate confidence; RCTs show ~15–20% cognitive improvement, but small samples limit generalizability.
  2. Anxiety Curcumin may reduce anxiety by modulating serotonin in brain neurons and lowering cortisol in adrenal cells. RCTs (500 mg/day, 8 weeks) show ~20% reduction in anxiety scores (HAM-A) via NF-κB inhibition in amygdala. Moderate confidence; small trials suggest benefits, but larger studies needed.
  3. Depression Curcumin improves depression by enhancing serotonin and BDNF in hippocampal neurons. RCTs (500–1000 mg/day, 6 weeks) show ~20% HAM-D reduction via monoaminergic modulation. Moderate confidence; effective as adjunct to antidepressants, but standalone data limited.
  4. Insomnia Curcumin may improve sleep by reducing oxidative stress in brain cells and modulating GABA in neurons. Preclinical studies show enhanced sleep quality via serotonin pathways. Low confidence; no human RCTs, but anxiety reduction may indirectly aid sleep.
  5. Alzheimer’s Disease Curcumin reduces amyloid-β plaques in neurons and enhances BDNF, slowing cognitive decline. RCTs (90–500 mg/day, 6–12 months) show improved memory and reduced tau in hippocampus. Moderate confidence; early trials promising, but larger studies needed.
  6. Fatigue Curcumin may alleviate fatigue by reducing oxidative stress in muscle and brain cells. Preclinical studies show mitochondrial support, lowering fatigue in fibromyalgia models. Low confidence; no human RCTs, but metabolic benefits may indirectly help.
  7. Gut Health Curcumin supports gut health by reducing mucosal inflammation in intestinal cells. RCTs (1000–2000 mg/day, 8 weeks) show improved remission in IBD via lowered TNF-α. High confidence; effective for IBS/IBD symptoms.
  8. Metabolic Health Curcumin improves metabolic health by activating AMPK in liver and muscle cells, enhancing insulin sensitivity. RCTs (500–1500 mg/day, 12 weeks) show ~10–20% glucose reduction in diabetes. High confidence; reduces Type-2 diabetics (T2DM) risk.  In a study of T2DM  adults, subjects received 80 mg of nano-curcumin capsules (Meriva) for 8 weeks.  Supplementation resulted in a significant reduction in glycated hemoglobin(HbA1c)  and Fasting Blood Sugar(FBS).
  9. Cardiovascular Health Curcumin lowers cardiovascular risk by reducing LDL oxidation in vascular cells and improving endothelial function. RCTs (500–2000 mg/day, 8 weeks) show ~10–15% LDL reduction. Moderate confidence; supports atherosclerosis prevention.
  10. Other pertinent relevant conditions

Cancer Prevention: Curcumin inhibits tumor growth via NF-κB and COX-2 in various cancers (preclinical, early trials). Low confidence for human use.

7. Synergies

  1. Prescription & OTC Medications
    • Vitamin B complex – numerous studies support a synergistic benefit with the use of supplemental B vitamins, most importantly vitamin B1, vitamin B2, vitamin B5, vitamin B6 and vitamin B12.
    • NSAIDS – Curcumin enhances NSAIDs in osteoarthritis (500 mg/day + diclofenac, ~30% better pain relief) by inhibiting COX-2 synergistically.
    • Gabapentin – With gabapentin in neuropathy, curcumin (1000 mg/day) may reduce oxidative stress, but data are preclinical.
    • 0pioids, curcumin delays tolerance by modulating glutamate receptors.
    • NACVAN® –  in addition to gabapentinoids, has been reported on a preliminary study to reduce pain severity in adult patients with spinal cord injury (SCI) or stroke-related central nerve pain syndrome. The Italian study published in 2022 evaluated a single dose of NACVAN® containing NAC (300 mg), Curcuma longa extract (211 mg), Boswellia serrata extract (200 mg), and vitamins B1(10 mg), B6 (5 mg), and B12 (2.5 mcg) administered twice daily for 6 weeks while concurrent dosing with either gabapentin or pregabalin or also administered. Each of the compound contain in neck. Van have demonstrated potential benefits for nerve pain in early studies. This combination of compounds is safe and consideration could be given to supplementing with any or all of these compounds in an effort to improve nerve pain.
  2. Nutraceuticals – Curcumin synergizes with other Nrf2 activators such as resveratrol for antioxidant effects (Nrf2 activation) in cognitive health.
    • EGCG (Matcha, green tea)
    • Quercetin, it reduces inflammation in gut health.
    • Alpha lipoic acid (ALA) enhances neuroprotection
    • Omega-3s (salmon) lower inflammatory cytokines
  3. Adaptogens – With ashwagandha, curcumin enhances stress reduction and anti-inflammatory effects for anxiety/depression. Rhodiola synergizes for fatigue via AMPK activation.
  4. Cannabinoids – THC/CBD with curcumin reduce pain via CB2 receptors and NF-κB in preclinical neuropathy.
  5. Terpenes – Beta-caryophyllene (black pepper) enhances curcumin’s anti-inflammatory effects via CB2 activation in osteoarthritis.
  6. Omega-3 Fatty Acids (EPA + DPA) – The findings of a 2024 study fnd that 12-week supplementation with EPA+DPA and nano-curcumin positively impact inflammation, oxidative stress, and metabolic parameters in patients with diabetes.
  7. Acupuncture Curcumin with acupuncture (LI4, ST36) may enhance pain relief in osteoarthritis via cytokine reduction.

8. Drug Interactions with Curcumin

  • Curcumin can interact with anticoagulants (e.g., warfarin), increasing bleeding risk by inhibiting platelet aggregation. With antidiabetic drugs, curcumin lowers glucose, potentially causing hypoglycemia. For chemotherapy (e.g., paclitaxel), curcumin may alter efficacy via CYP3A4 inhibition. In liver metabolism, curcumin inhibits CYP enzymes, affecting drugs like statins or antidepressants. Consult a doctor for monitoring; enhanced forms may amplify interactions.
  • While the clinical significance has not yet been established, curcumin has been shown to inhibit P-gp, a transporter that affects blood levels and central nervous system levels of certain drugs. As a result of this inhibition, it may be possible that curcumin can decrease blood levels but at the same time increase central nervous levels of fentanyl, morphine, methadone and possibly oxycodone. This could result in either increased or decreased therapeutic effect and/or side effects. When taking curcumin while also taking these medications, caution should be emphasized by monitoring for changes in responsiveness to the medications and it may be necessary to reduce the dose of these medications to avoid side effects.

9. Recommended Dosing

Dietary sources (insufficient for therapeutic benefits)

Curcumin is primarily found in turmeric (Curcuma longa) and curry powders, providing low doses insufficient for therapeutic effects compared to supplements (500–2000 mg/day). Concentrations vary due to cultivar, region, and processing (e.g., drying, cooking).

Curcumin Content per 100 g (3.5 oz):

  • Turmeric Root (Fresh): 20–180 mg/100 g (higher in high-curcumin varieties).
  • Turmeric Powder: 20–100 mg/100 g (1–2 tsp ~2–5 g provides 40–200 mg).
  • Curry Powder: 10–50 mg/100 g (varies by turmeric content).
  • Ginger Root: Trace amounts (<5 mg/100 g).

Dietary Considerations:

  • Values vary due to processing (e.g., drying reduces content) and cultivar.
  • Dietary intake (e.g., 1 tsp turmeric) provides <200 mg/day, below therapeutic doses.
  • Cooking with fat/piperine enhances absorption.

Supplement Doses

  • Curcumin supplements are available in various forms to overcome low bioavailability (<1% for standard curcumin).
  • Recommended doses range from 500–2000 mg/day, with enhanced formulations (Liposomal or Nanoparticle) preferred.
  • Liposomal or nanoparticle forms are ideal for brain delivery

Start low (500 mg/day) for pain or cognitive benefits, increasing as tolerated. Take with meals containing fat for better absorption.

For osteoarthritis, 500–1500 mg/day (8–12 weeks) shows ~20–30% pain reduction.

For gut health, 1000–2000 mg/day improves IBD remission.

For cognitive function, 90–500 mg/day enhances memory. Liposomal or nanoparticle forms are ideal for brain delivery in Alzheimer’s. Monitor for GI upset at >4 g/day.

Safety

Curcumin is safe at 500–2000 mg/day, with mild GI upset (e.g., nausea, diarrhea) at high doses (>4 g/day). Rare liver toxicity reported in sensitive individuals. Contraindications: Gallbladder issues (may stimulate bile production); pregnancy (limited data). Interactions: Enhances blood thinners (e.g., warfarin), diabetes drugs (lowers glucose), or chemotherapy (may interfere). Consult doctor for long-term use or with medications.

10. Bioavailability and Recommended Formulations

10a Bioavailability

Curcumin’s bioavailability is low (<1%) due to poor solubility, rapid metabolism (glucuronidation in liver/intestines), and quick excretion. Absorption occurs in the gut, but most is metabolized before systemic circulation. Factors affecting uptake include dose, formulation, and co-ingestion with fats/piperine. Empty stomach intake reduces absorption; proteins may hinder uptake. Enhanced formulations  increase plasma levels ~20-fold. For brain penetration in neuropathy/Alzheimer’s, nanoparticle forms improve BBB crossing. Practical dosing: 500–2000 mg/day with enhancers for therapeutic effects.

In summary, liposomal’s lipid-based delivery better targets brain uptake, while nanoparticle’s design better targets systemic tissues, for an in-depth review comparing liposomal versus nano particle formulations, See: Liposomal vs. Nanoparticle Curcumin Recommendations

 

10b Formulations

Standard Curcumin: Unformulated capsules/powders.

    • Strengths: Affordable (~$0.10–$0.20/g).
    • Weaknesses: Poor absorption (<1%).

Piperine-Enhanced (e.g., BioPerine)

    • Increases absorption ~20-fold.
    • Strengths: Cost-effective, effective for pain (500–1000 mg/day).
    • Weaknesses: Piperine may interact with drugs.

Liposomal Curcumin:

    • Best For: Cognitive function, Alzheimer’s, gut health 
    • (200–500 mg/day)
    • Improves bioavailability 5–10-fold.
    • Strengths: Superior penetration nto the brain, sustained release, effective at lower doses for brain and central nervous system benefits (e.g., Alzheimer’s, cognition), also supports gut health
    • Weaknesses: Expensive (~$0.50–$1/g), variable quality across brands, less evidence than nanoparticle formulations for pain with fewer  research studies (RCTs) for CNS outcomes.

Nanoparticle Curcumin [e.g., Theracurmin (5-fold > Meriva) ]: 10–30-fold absorption > standard.

    • Best For: Chronic pain, Systemic Inflammation
    • 150–500 mg/day
    • Strengths: Targeted delivery for osteoarthritis/neuropathy, more research evidence supporting benefits
    • Weaknesses: Costly (~$0.40–$0.80/g).

Micellar Curcumin: >100-fold absorption.

    • Strengths: Low-dose efficacy (100–200 mg/day).
    • Weaknesses: Expensive (~$1–$2/g), limited data.

 

  • Recommendation:
    • Piperine-enhanced for general use
    • Nanoparticle for chronic pain
    • Liposomal for cognitive function, Alzheimer’s, gut health
  • Practical tips:
    1. Take with fatty meals/piperine to enhance absorption.
    2. Avoid protein-rich meals to prevent binding.
    3. Split doses (morning/evening) for steady levels.
    4. Use black pepper (piperine) in cooking for dietary curcumin.
    5. Monitor for GI upset; start with low dose (500 mg/day).

11 Mechanisms of Action 

11a. Mechanisms of Action – Patient-Friendly Explanation

Curcumin reduces swelling in joints and nerves, protects your brain, and supports digestion, energy, and heart health, easing pain, mood, and memory.

11b Mechanisms of Action – Physician-Level Explanation (up to 500 words per subsection)

Curcumin’s antioxidant activity upregulates Nrf2 in cells, boosting SOD, glutathione, and catalase, reducing ROS in chondrocytes and neurons. Anti-inflammatory effects inhibit NF-κB and COX-2, lowering IL-6 and TNF-α in synovial and immune cells. Neuroprotection reduces amyloid-β and enhances BDNF in hippocampal neurons for Alzheimer’s. Metabolic/cardiovascular benefits activate AMPK in liver/muscle cells, lowering LDL in vascular endothelium.

12. Levels of Confidence 

For an explanation of what “Levels of Confidence” is based on, See: Levels of Confidence in Scientific Studies

Determining Levels of Confidence

Levels of confidence are determined by the hierarchy of research study designs:

  • Randomized Controlled Trials (RCTs): High confidence (e.g., a drug for diabetic neuropathy [1]). Randomized Controlled Trials (RCTs) involve human participants who are randomly assigned to different groups (treatment or control) to test the effectiveness of an intervention.Limitations: Short duration.
  • Systematic Reviews/Meta-Analyses: Highest confidence (e.g., diabetic neuropathy meta-analysis [1]).
  • Cochrane Reviews: Gold-standard systematic reviews.
  • Other Studies: Observational, preclinical; lower confidence (e.g., acute pain [4]). Confidence is rated High (robust RCTs, meta-analyses), Moderate (small RCTs, observational), or Low (preclinical, case reports).

Levels of Confidence in Omega-3s research

  • Osteoarthritis: High confidence; multiple RCTs and meta-analyses show ~20–30% pain reduction.
  • Rheumatoid Arthritis: Moderate confidence; RCTs indicate inflammation reduction, but small samples.
  • Gut Health: High confidence; RCTs confirm remission in IBD.
  • Metabolic Health: High confidence; meta-analyses show glucose reduction.
  • Cardiovascular Health: Moderate confidence; RCTs show LDL/blood pressure reduction, varying doses.
  • Cognitive Function: Moderate confidence; RCTs show memory improvement, limited long-term data.
  • Depression: Moderate confidence; RCTs show mood improvement, adjunctive use.
  • Systemic Inflammation: High confidence; consistent RCT reductions in CRP/IL-6.
  • Oxidative Stress: High confidence; RCTs and preclinical show ROS reduction.
  • Neuropathy/MS/Migraines/Anxiety/Insomnia/Alzheimer’s/Fatigue: Low to Moderate; mostly preclinical or pilot data.
  • Safety/Bioavailability: High confidence; robust data, enhanced forms recommended.

13. Chemistry and Sources

  • Chemical structure: Curcumin (C21H20O6, diferuloylmethane) is a polyphenolic compound with a bright yellow color, responsible for turmeric’s properties.
  • Primary dietary sources: Turmeric root (20–180 mg/100 g fresh, higher in select varieties); turmeric powder (20–100 mg/100 g); curry powder (10–50 mg/100 g); ginger root (trace <5 mg/100 g). Dietary intake (~100 mg/day from cooking) is below therapeutic levels.

14. Patient Handout

Curcumin: Your Natural Pain and Inflammation Reliever

What is Curcumin?

  • Curcumin is the main active ingredient in turmeric, a spice used in cooking. It helps reduce swelling and pain in your body.

How Does It Help?

  • Joint Pain: Reduces pain in arthritis.
  • Nerve Pain: May help with diabetic nerve pain.
  • Mood: Improves anxiety and depression.
  • Brain Health: Helps memory and protects against Alzheimer’s.
  • Gut Health: Supports digestion and reduces gut issues.
  • Heart Health: Lowers cholesterol and blood pressure.

How to Get It?

  • Diet: Add turmeric to food (1 tsp provides ~100 mg).
  • Supplements: 500–2000 mg/day in liposomal forms.
  • Safety: Mild stomach upset possible; check with your doctor.

Curcumin

Curcumin

LOC: High

Curcumin is the active compound in turmeric

Dosing: 1000 mg per day as monotherapy

Poor oral bioavailability, requires enhancement for proper absorption:

    • Ingest with black pepper
    • phytosomal or nano-formulations

Special Considerations:

  • Anti-inflammatory comparable benefit to NSAID diclofenac (Voltaren) in knee osteoarthritis but with less side effects
  • Drug interactions may be comparable to other anti-inflammatory medications including: Antiplatelets, anticoagulants, thrombolytic agents, NSAIDs/salicylates

 

Curcumin

People throughout Asia have benefited from the healthful effects of curcumin for centuries. Curcumin is the orange pigment in turmeric (the primary ingredient in curry), and is a potent antioxidant that offers numerous health benefits, including supporting joint health and hepatic, GI, and cardiovascular function by helping to maintain the body’s normal infIammatory response.

Several studies have illustrated curcumin’s liver-protective effects, leading researchers to suggest its use in protecting the liver from environmental toxins.  Curcumin’s liver-protective effects are due in part to direct free-radical scavenging; but as a NRF2 activator curcumin also enhances the body’s natural antioxidant system.

 

Formulations to enhance absorption and bioavailability

Phytosomal Curcumin

Whether taken as a supplement or from food, curcumin is generally poorly absorbed into the bloodstream so formulations designed to enhance absorption are highly recommended. One option is the use of phytosomes.  Phytosomes are plant extracts bound to phosphatidylcholine (PC), an essential component of human cells. Our bodies can make PC, but it can also be obtained from food or supplements. When taken orally, PC is very well absorbed so when curcumin is attached to PC it achieves superior absorption. Meriva-500 is a unique, patented phytosomal curcumin product that comes highly recommended.

Studies have demonstrated up to a >20-fold increase in absorption with phytosomal curcumin compared to standard curcumin preparations. In addition, a 2010 three-month clinical trial demonstrated 1,000 mg of phytosomal curcumin/day  promoted healthy joint comfort and mobility and helped maintain healthy C-reactive protein levels.

Drug Interactions with Curcumin

While the clinical significance has not yet been established, curcumin has been shown to inhibit P-gp, a transporter that affects blood levels and central nervous system levels of certain drugs. As a result of this inhibition, it may be possible that curcumin can decrease blood levels but at the same time increase central nervous levels of fentanyl, morphine, methadone and possibly oxycodone. This could result in either increased or decreased therapeutic effect and/or side effects. When taking curcumin while also taking these medications, caution should be emphasized by monitoring for changes in responsiveness to the medications and it may be necessary to reduce the dose of these medications to avoid side effects.

* These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

 

Meriva (curcumin)

Meriva 500 mg

Suggested dose: Take 1-2 capsules two times daily.

 

Purchasing Supplements

When purchasing supplements reviewed on this web site and discussed with Dr. Ehlenberger, a discount on usual commercial pricing can be obtained by purchasing from Accurate Clinic’s online Supplement Store after acquiring the discount code from Accurate Clinic:

 

Accurate Clinic’s Supplement Store

or call Toll-Free: 877-846-7122 (Option 2)

Reference Publications:

 

Curcumin –  Overview

  1. Anti-inflammatory Properties of Curcumin, a Major Constituent of Curcuma longa_ A Review of Preclinical and Clinical Research
  2. Therapeutic roles of curcumin – lessons learned from clinical trials. – 2013
  3. Turmeric – NCCIH 2012
  4. effects-of-curcumin-on-ion-channels-and-transporters-2014
  5. Curcumin – A Review of Its’ Effects on Human Health – 2017
  6. Therapeutic Effects of Phytochemicals and Medicinal Herbs on Chemotherapy-Induced Peripheral Neuropathy – 2016
  7. Key Developments in the Potential of Curcumin for the Treatment of Peripheral Neuropathies – 2020

 

 

Curcumin – Carpal Tunnel Syndrome CTS

  1. Oral Supplementation with Alpha-Lipoic Acid, Curcumin Phytosome, and B-Group Vitamins in Patients with Carpal Tunnel Syndrome

Curcumin – Diabetes

  1. Curcumin and diabetes – a systematic review – 2013
  2. Meriva®, a lecithinized curcumin delivery system, in diabetic microangiopathy and retinopathy – 2012
  3. Potential role of curcumin phytosome (Meriva) in controlling the evolution of diabetic microangiopathy. – pilot study – 2010
  4. Curcumin Pharmacokinetic and Pharmacodynamic Evidences in Streptozotocin-Diabetic Rats Support the Antidiabetic Activity to Be via Metabolite(s) – 2015
  5. Spice-Derived Bioactive Ingredients – Potential Agents or Food Adjuvant in the Management of Diabetes Mellitus – 2018
  6. Curcumin as a promising therapeutic agent for diabetic neuropathy_ from molecular mechanisms to functional recovery – PubMed – 2025
  7. The effect of curcumin and high-content eicosapentaenoic acid supplementations in type 2 diabetes mellitus patients- a double-blinded randomized clinical trial – 2024

 

Curcumin – Drug Interactions

  1. Overview of P-glycoprotein inhibitors – a rational outlook – 2012
  2. Emerging Significance of Flavonoids as P-Glycoprotein Inhibitors in Cancer Chemotherapy – 2009
  3. Herbal modulation of P-glycoprotein. [Drug Metab Rev. 2004] – PubMed – NCBI
  4. modulation-of-p-glycoprotein-expression-and-function-by-curcumin-in-multidrug-resistant-human-kb-cells-pubmed-ncbi
  5. osthol-and-curcumin-as-inhibitors-of-human-pgp-and-multidrug-efflux-pumps-of-staphylococcus-aureus-reversing-the-resistance-against-frontline-antibacterial-drugs-2014

Curcumin – Gastrointestinal Disease

  1. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases – 2018
  2. Curcumin – A Potent Protectant against Esophageal and Gastric Disorders – 2019

Curcumin – Curcumin

  1. Curcumin Suppression of Cytokine Release and Cytokine Storm – A Potential Therapy for Patients with Ebola and Other Severe Viral Infections – 2015
  2. Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF-κB signaling pathway – 2017
  3. Anti-infective Properties of the Golden Spice Curcumin – 2019

 

Curcumin – Liver Disease

  1. Antioxidants in liver health – 2015
  2. Modulatory effects of curcumin, silybin-phytosome and alpha-R-lipoic acid against thioacetamide-induced liver cirrhosis in rats

Curcumin – Morphine Tolerance

  1. Curcumin attenuates opioid tolerance and dependence by inhibiting Ca2+:calmodulin-dependent protein kinase II α activity. – PubMed – NCBI
  2. Orally Administered Nano-curcumin to Attenuate Morphine Tolerance – 2013

Curcumin – Liposomal and Nanoformulations

  1. Comparative Absorption of a Standardized Curcuminoid Mixture and Its Lecithin Formulation – 2011
  2. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine – Springer
  3. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. – 2012
  4. Nanotechnology-Applied Curcumin for Different Diseases Therapy – 2014
  5. Getting into the brain – liposome-based strategies for effective drug delivery across the blood–brain barrier – 2016
  6. Use of Lipid Nanocarriers to Improve Oral Delivery of Vitamins – 2019
  7. Randomized pharmacokinetic cross-over study comparing two curcumin preparations in plasma and rectal tissue of healthy human volunteers – 2017
  8. Phospholipid Complex Technique for Superior Bioavailability of Phytoconstituents – 2017
  9. Bioavailability and activity of phytosome complexes from botanical polyphenols – the silymarin, curcumin, green tea, and grape seed extracts. – 2009
  10. Liposomal Curcumin is Better than Curcumin to Alleviate Complications in Experimental Diabetic Mellitus 0 2019

Curcumin – Neuropathy

  1. Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and:or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen

 

Curcumin – Obesity

  1. Curcumin and obesity. – PubMed – NCBI
  2. Curcumin and obesity: evidence and mechanisms. – PubMed – NCBI
  3. Curcumin and resveratrol inhibit nuclear factor-kappaB-mediated cytokine expression in adipocytes – 2008
  4. Inflammation-mediated obesity and insulin resistance as targets for nutraceuticals. – PubMed – NCBI
  5. Targeting Inflammation-Induced Obesity and Metabolic Diseases by Curcumin and Other Nutraceuticals – 2010

Curcumin – Opioid Induced Hyperalgesia (OIH) & Tolerance

  1. Curcumin blocks chronic morphine analgesic tolerance and brain-derived neurotrophic factor upregulation. – PubMed – NCBI

 

Curcumin – Ophthalmology

Central Serous Chorioretinopathy

  1. Oral administration of a curcumin-phospholipid delivery system for the treatment of central serous chorioretinopathy – a 12-month follow-up study
  2. Pilot study of oral administration of a curcumin- phospholipid formulation for treatment of central serous chorioretinopathy -2012

Curcumin – Oral dental

  1. Effectiveness of Curcumin in Reducing Self-Rated Pain-Levels in the Orofacial Region- A Systematic Review of Randomized-Controlled Trials – 2022

 

Curcumin – Osteoarthritis

  1. Biological actions of curcumin on articular chondrocytes – 2009
  2. Efficacy and Safety of Meriva®, a Curcumin-phosphatidylcholine Complex, during Extended Administration in Osteoarthritis Patients
  3. Product-evaluation registry of Meriva®, a curcumin-phosphatidylcholine complex, for the complementary management of osteoarthritis – 2010
  4. Efficacy and Safety of Curcuma domestica Extracts in Patients with Knee Osteoarthritis – 2009
  5. Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis – A Systematic Review and Meta-Analysis of Randomized Clinical Trials – 2016

 

Curcumin – Oxidative Stress

  1. Spinal glial activation and oxidative stress are alleviated by treatment with curcumin or coenzyme Q in sickle mice

 

Curcumin – Pain

  1. Comparative evaluation of the pain-relieving properties of a lecithinized formulation of curcumin (Meriva®), nimesulide, and acetaminophen – 2013 no highlights
  2. Reduction of delayed onset muscle soreness by a novel curcumin delivery system (Meriva®) – 2014

Curcumin – Piperine (Black Pepper)

  1. Piperine, a Natural Bioenhancer, Nullifies the Antidiabetic and Antioxidant Activities of Curcumin in Streptozotocin-Diabetic Rats – 2014

 

Curcumin – Prostate Disease

  1. Inhibitory effect of curcumin on testosterone induced benign prostatic hyperplasia rat model – 2015
  2. Meriva®, a lecithinized curcumin delivery system, in the control of benign prostatic… – Abstract – Europe PubMed Central

Curcumin – Synergies

  1. A Nutritional Supplement as Adjuvant of Gabapentinoids for Adults with Neuropathic Pain following Spinal Cord Injury and Stroke- Preliminary Results – 2023

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.